query: What are the longer-term complications of those who recover from COVID-19?

positive: The impact of nutrition on COVID-19 susceptibility and long-term consequences Abstract While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type II diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.

positive: Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada? INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

positive: Cardiac involvement in COVID-19 patients: Risk factors, predictors, and complications: A review BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID-19. RESULTS: Notably, COVID-19 patients with pre-existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID-19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID-19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID-19 patients to promote more informed treatment and, ultimately, better clinical outcomes.

positive: A complication of coronavirus disease 2019: delirium COVID-19 is predominantly a respiratory disease. However, some cases exhibit other features including Central Nervous System symptoms. In the older adult, COVID-19 may present with atypical symptoms, including delirium and its complications. The objective of this study is to describe the relationship between the new type of coronavirus infection and delirium. Systematic research (Cochrane Library and PubMed) was carried out (only upper time limit: April 2020). Publications found through this indexed search were reviewed and manually screened to identify relevant studies. Search terms used included “COVID-19, Delirium, Dementia, Intensive Care Unit”. We manually added articles identified through other sources (i.e., key journals). Older people are at the greatest risk from COVID-19. If infected, they may present delirium. Moreover, it is not exclusive to older people. Delirium is not inevitable; rather, it is preventable. Delirium prevention programs are even more crucial in the era of COVID-19 and cannot be allowed to wither despite the challenges of integrating delirium prevention with COVID-19 care. An acute change in condition, behaviour, or mental status should prompt a delirium screen. As regards the treatment, it is advisable to use non-pharmacological interventions first where possible. Medication may be needed for patients with agitation where there is intractable distress or high risk to self/others.

positive: Patients who have recovered from covid-19: issuing certificates and offering voluntary registration.

positive: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19) Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.

positive: Clinical Features of COVID-19 Related Liver Damage BACKGROUND: A recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODS: In this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay. FINDINGS: Of 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission, characterized by an increased of alt, ast, GGT, AKP. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay. INTERPRETATION: SARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.

positive: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China Abstract Background A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. Methods We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. Results 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. Conclusions The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.

positive: Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.

positive: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications ? Abstract COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males. Background With increasing number of COVID-19 cases, an evident sex- dependent difference in disease outcomes can be observed. Based on published studies with short term follow-up, males have 65% higher mortality rate (1). The question remains, whether long term observational studies will confirm improved recovery in females.

positive: Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis OBJECTIVE: To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES: Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION: Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION: Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months after hospital discharge, and beyond 6 months after discharge. DATA SYNTHESIS: Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months after discharge were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 1545%); and reduced exercise capacity (mean 6-min walking distance 461 m, CI 450473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 3147%), depression (33%, 95% CI 2050%) and anxiety (30%, 95% CI 1061) beyond 6 months after discharge were considerable. Low scores on Short-Form 36 were identified beyond 6 months after discharge. CONCLUSION: Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.

positive: [SARS-CoV-2 infection (COVID-19): what can we expect?] - Case numbers in China are clearly declining, case numbers in many European regions are no longer increasing exponentially.- Data on mortality from SARS-CoV-2 infection are contradictory; mortality is certainly lower than for SARS and MERS, but probably higher than for most seasonal flu outbreaks in recent years- The main complication of SARS-CoV-2 infection is pneumonia with development of acute respiratory distress syndrome (ARDS)- Asymptomatic and oligosymptomatic courses with virus shedding are not uncommon; they may be more frequent in children than in adults. Virus excretion in asymptomatic people and in the pre-symptomatic phase of an infection is relevant for transmission- An effective antiviral therapy has not yet been established. Steroids for anti-inflammatory therapy are not recommended- It is very important to prepare all actors in the health care system for a longer-term burden of inpatients and complications and to create the necessary capacities. Low-threshold diagnostic testing and rapid detection of infection chains remain essential for better control of the pandemic. An effective vaccine is urgent.

positive: Olfactory dysfunction in recovered COVID‐19 patients

positive: Coronaviruses and the cardiovascular system: acute and long-term implications.

positive: A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence Abstract The pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 is a highly contagious disease. The World Health Organization (WHO) has declared the ongoing outbreak as a global public health emergency. Currently, the research on novel coronavirus is still in the primary stage. Based on the current published evidence, we systematically summarizes the epidemiology, clinical characteristics, diagnosis, treatment and prevention of knowledge surrounding COVID-19. This review in the hope of helping the public effectively recognize and deal with the 2019 novel coronavirus (SARS-CoV-2), and providing a reference for future studies.

positive: De Novo Status Epilepticus in patients with COVID-19 Neurological complications are increasingly recognized with SARS-CoV-2, the causative pathogen for COVID-19. We present a single-center retrospective case series reporting the EEG and outcome of de novo status epilepticus (SE) in two African-American women with laboratory-confirmed SARS-CoV-2 virus. SE was the initial presentation in one asymptomatic individual. Patient 2 had COVID-19 pneumonia, and fluctuating mental status that raised the suspicion of subclinical SE. The patient with older age and higher comorbidities failed to recover from the viral illness that has no definitive treatment.

positive: Preliminary detection of lung hypoperfusion in discharged Covid-19 patients during recovery

positive: Mental health and a novel coronavirus (2019-nCoV) in China

positive: COVID-19 Pandemic: Cardiovascular Complications and Future Implications Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.

positive: Recurrence of positive SARS-CoV-2 in patients recovered from COVID-19

positive: Three further ways that the COVID-19 pandemic will affect health outcomes

positive: Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05–1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44–9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3–5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0–4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.

positive: Clinical features and the maternal and neonatal outcomes of pregnant women with coronavirus disease 2019 BACKGROUND There is little information about the coronavirus disease 2019 (Covid-19) during pregnancy. This study aimed to determine the clinical features and the maternal and neonatal outcomes of pregnant women with Covid-19. METHODS In this retrospective analysis from five hospitals, we included pregnant women with Covid-19 from January 1 to February 20, 2020. The primary composite endpoints were admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Secondary endpoints included the clinical severity of Covid-19, neonatal mortality, admission to neonatal intensive care unit (NICU), and the incidence of acute respiratory distress syndrome (ARDS) of pregnant women and newborns. RESULTS Thirty-three pregnant women with Covid-19 and 28 newborns were identified. One (3%) pregnant woman needed the use of mechanical ventilation. No pregnant women admitted to the ICU. There were no moralities among pregnant women or newborns. The percentages of pregnant women with mild, moderate, and severe symptoms were 13 (39.4%),19(57.6%), and 1(3%). One (3.6%) newborn developed ARDS and was admitted to the NICU. The rate of perinatal transmission of SARS-CoV-2 was 3.6%. CONCLUSIONS This report suggests that pregnant women are not at increased risk for severe illness or mortality with Covid-19 compared with the general population. The SARS-CoV-2 infection during pregnancy might not be associated with as adverse obstetrical and neonatal outcomes that are seen with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy. (Funded by the National Key Research and Development Program.)

positive: Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: dynamic results from 108 days of follow-up The evidence of long-term clinical dynamic on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA re-positive case are less. We performed a 108 days follow-up on dynamic clinical presentations in a case, who hospitalized three times due to the positive recurrence of SARS-CoV-2 RNA after discharge, to understand the prognosis of the 2019-Coronavirus disease (COVID-19). In this case, positive SARS-CoV-2 recurred even after apparent recovery (normal CT imaging, no clinical symptoms, negative SARS-CoV-2 on stool sample and negative serum IgM test) from COVID-19, viral shedding duration lasted for 65 days, the time from symptom onset to disappearance was up to 95 days. Erythrocyte-associated indicators, liver function and serum lipid metabolism presented abnormal throughout during the observation period. Awareness of atypical presentations such as this one is important to prompt the improvement of the management of COVID-19.

positive: Infectivity of human coronavirus in the brain A new strain of human coronaviruses (hCoVs), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been identified to be responsible for the current outbreak of the coronavirus disease 2019 (COVID-19). Though major symptoms are primarily generated from the respiratory system, neurological symptoms are being reported in some of the confirmed cases, raising concerns of its potential for intracranial invasion and neurological manifestations, both in the acute phase and in the long-term. At present, it remains unclear the extent to which SARS-CoV-2 is present in the brain, and if so, its pathogenic role in the central nervous system (CNS). Evidence for neuroinvasion and neurovirulence of hCoVs has been recognised in animal and human studies. Given that SARS-CoV-2 belongs to the same family and shares characteristics in terms of receptor binding properties, it is worthwhile exploring its potential CNS manifestations. This review summarises previous findings from hCoVs in relation to the CNS, and compares these with the new strain, aiming to provide a better understanding of the effects of SARS-CoV-2 on the CNS.

positive: Patient Follow‐up after Discharge after COVID‐19 Pneumonia: Considerations for Infectious Control Coronavirus disease 2019 (COVID‐19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID‐19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID‐19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long‐term pulmonary defects, and post‐traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID‐19 for reference to come to a consensus on follow‐up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long‐term follow‐up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.

positive: Reactive psychoses in the context of the COVID-19 pandemic: clinical perspectives from a case series Abstract Introduction: The world is currently undergoing an extremely stressful scenario due to the COVID-19 pandemic. This unexpected and dramatic situation could increase the incidence of mental health problems, among them, psychotic disorders. The aim of this paper was to describe a case series of brief reactive psychosis due to the psychological distress from the current coronavirus pandemic. Materials and methods: We report on a case series including all the patients with reactive psychoses in the context of the COVID-19 crisis who were admitted to the Virgen del Rocío and Virgen Macarena University Hospitals (Seville, Spain) during the first two weeks of compulsory nationwide quarantine. Results: In that short period, four patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a brief reactive psychotic disorder. All of the episodes were directly triggered by stress derived from the COVID-19 pandemic and half of the patients presented severe suicidal behavior at admission. Conclusions: We may now be witnessing an increasing number of brief reactive psychotic disorders as a result of the COVID-19 pandemic. This type of psychosis has a high risk of suicidal behavior and, although short-lived, has a high rate of psychotic recurrence and low diagnostic stability over time. Therefore, we advocate close monitoring in both the acute phase and long-term follow-up of these patients.

positive: Establishment of a COVID-19 Recovery Unit in a Veteran Affairs (VA) Post-Acute Facility Coronavirus disease 19 (COVID-19) is now an epidemic of global proportion with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long-term care facilities. This health catastrophe has challenged healthcare facilities' capacity to deliver care to not only COVID-19 patients but all patients who need hospital care. We report on a novel approach of utilizing long-term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID-19 patients.

positive: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of “post-COVID-19 Cardiac Syndrome”

positive: Proyección epidemiológica de COVID-19 en Chile basado en el modelo SEIR generalizado y el concepto de recuperado./ [An epidemiological forecast of COVID-19 in Chile based on the generalized SEIR model and the concept of recovered] The COVID-19 pandemic declared by the World Health Organization (WHO) has generated a wide-ranging debate regarding epidemiological forecasts and the global implications. With the data obtained from the Chilean Ministry of Health (MINSAL), a prospective study was carried out using the generalized SEIR model to estimate the course of COVID-19 in Chile. Three scenarios were estimated: Scenario 1 with official MINSAL data; scenario 2 with official MINSAL data and recovery criteria proposed by international organizations of health; and scenario 3 with official MINSAL data, recovery criteria proposed by international organizations of health, and without considering deaths in the total recovered. There are considerable differences between scenario 1 compared to 2 and 3 in the number of deaths, active patients, and duration of the disease. Scenario 3, considered the most adverse, estimates a total of 11,000 infected people, 1,151 deaths, and that the peak of the disease will occur in the first days of May. We concluded that the concept of recovered may be decisive for the epidemiological forecasts of COVID-19 in Chile.

positive: Chest CT features and their role in COVID-19 Abstract Since December 2019, the novel coronavirus disease (COVID-19) has spread rapidly throughout China. This article reviews the chest CT features of COVID-19 and analyzes the role of chest CT in this health emergency.

positive: Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19. This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.

positive: A Contemporary Review of Neurological Sequelae of COVID-19 Coronavirus 2019 (COVID-19) is currently the center of what has become a public health crisis. While the virus is well-known for its trademark effects on respiratory function, neurological damage has been reported to affect a considerable proportion of severe cases. To characterize the neuro-invasive potential of this disease, a contemporary review of COVID-19 and its neurological sequelae was conducted using the limited, but growing, literature that is available. These neurological squeal are based on the manifestations that the virus has on normal central and peripheral nervous system function. The authors present the virology of the SARS-CoV-2 agent by analyzing its classification as an enveloped, positive-stranded RNA virus. A comprehensive timeline is then presented, indicating the progression of the disease as a public health threat. Furthermore, underlying chronic neurological conditions potentially lead to more adverse cases of COVID-19. SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation. The CNS may also be susceptible to an immune response where a “cytokine storm” can manifest into neural injury. Histological evidence is provided, while symptoms such as headache and vertigo are highlighted as CNS manifestations of COVID-19. Treatment of these symptoms is addressed with paracetamol being recommended as a possible, but not conclusive, treatment to some CNS symptoms. The authors then discuss the peripheral nervous system sequelae and COVID's impact on causing chemosensory dysfunction starting with viral attack on olfactory sensory neurons and cells types within the lining of the nose. Histological evidence is also provided while symptoms such as anosmia and ageusia are characterized as PNS manifestations. Possible treatment options for these symptoms are then addressed as a major limitation, as anecdotal, and not conclusive evidence can be made. Finally, preventive measures of the neurological sequelae are addressed using a multidirectional approach. Postmortem examinations of the brains of COVID-19 patients are suggested as being a possible key to formulating new understandings of its neuropathology. Lastly, the authors suggest a more comprehensive neurological follow-up of recovered patients, in order to better characterize the neurological sequelae of this illness.

positive: Updates of Cardiovascular Manifestations in COVID-19: Korean Experience to Broaden Worldwide Perspectives The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Not just respiratory complications such as pneumonia and acute respiratory distress syndrome, cardiac manifestations have drawn attention due to the increased risk of mortality and morbidity related to SARS-CoV-2 infections. The mechanisms of the cardiac injury related to SARS-CoV-2 infections have been direct cardiac injury caused by angiotensin converting enzyme 2, hypoxemia, microvascular damage, and a systemic inflammatory response. Stress induced cardiomyopathy in a critically ill condition and acute coronary syndrome due to a vulnerable plaque rupture with coagulopathy can finally lead to acute heart failure with further cardiac manifestations. When dealing with the highly contagious viral disease-related cardiac manifestations, we should carefully apply the diagnostic and therapeutic methods to achieve the best therapeutic results without adding any risk of disease transmission.

positive: Cardiac involvement in recovered COVID-19 patients identified by magnetic resonance imaging Abstract Objective To evaluate cardiac involvement in recovered COVID-19 patients using cardiac MRI. Background Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19. Methods Twenty-six recovered COVID-19 patients that reported cardiac symptoms and underwent MRI exams were retrospectively included. MRI protocols consisted of conventional sequences (cine, T2WI, LGE), and quantitative mapping sequences (T1, T2, and ECV mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls. Results Fifteen patients (58%) had abnormal MRI findings on conventional MRI sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased RV functional parameters including EF, CI, and SV/ BSA were found in patients with positive conventional MRI findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional MRI findings, compared to patients without positive findings and controls (median [IQR], native T1 1271ms [1243-1298] vs 1237ms [1216-1262] vs 1224ms [1217-1245]; mean [SD], T2 42.7ms [3.1] vs 38.1ms [2.4] vs 39.1ms [3.1]; median [IQR], 28.2% [24.8-36.2] vs 24.8% [23.1-25.4] vs 23.7% [22.2-25.2]; p=0.002, p <0.001, and p =0.002, respectively). Conclusions Cardiac involvement was found in a proportion of the recovered COVID-19 patients. MRI manifestation included myocardial edema, fibrosis, and impaired RV function. Attention should be paid to the possible myocardial involvement in recovered COVID-19 patients with cardiac symptoms.

positive: Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods: A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results: A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. Conclusions Patients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

positive: Cardiological society of India position statement on COVID-19 and heart failure The COVID 19 global pandemic has engulfed humanity with a huge impact on health systems across the world. Many patients develop myocardial injury which can lead to significant cardiovascular complications including HF. This will require aggressive management strategies which are evolving. Guideline directed drug therapy including ACEI/ARB/ARNI is to be continued in patients with pre-existing HF. Long-term cardiovascular effects of COVID-19 are yet to be ascertained. Protection of health care personnel from contracting the disease should be given high priority.

positive: COVID-19: The potential treatment of pulmonary fibrosis associated with SARS-CoV-2 infection In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients’ quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.

positive: How to Detect and Track Chronic Neurologic Sequelae of Covid-19? Use of Auditory Brainstem Responses and Neuroimaging for Long-term Patient Follow-up This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.

positive: The place of early rehabilitation in ICU for Covid-19

positive: COVID‐19 in pregnancy: risk of adverse neonatal outcomes We read with great interest the study by Siyu Chen and colleagues. The authors evaluated the clinical features and outcomes of five pregnant patients with COVID‐19 at term, whose delivery was uneventful and led to favorable perinatal outcomes for both mother and neonate. We would like to draw attention to a growing body of evidence that now points towards an under‐addressed association between preterm maternal SARS‐CoV‐2 infection, preterm delivery and adverse neonatal outcomes, which is not reflected in Chen et al.'s small cohort. We also stress that vertical transmission, which was not tested for by Chen et al., should not be excluded as a potential mechanism for viral spread. Centers should therefore be meticulous in their approach to a SARS‐CoV‐2+ pregnancy to optimize clinical outcomes for both mother and child. This article is protected by copyright. All rights reserved.

positive: SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up–to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.

positive: Mental Health Care for Survivors and Healthcare Workers in the Aftermath of an Outbreak When pandemics sweep across communities, they leave behind tremendous suffering in their wake. It is not only the illness that becomes a pandemic, but the same can be inferred about fear, mourning, and despair. The reverberations of loss are felt in a multitude of ways by those left behind. Often times, the mental health issues of affected persons and entire communities do not receive the attention they deserve in the light of other competing, immediate needs imparted by the devastation of the pandemic. This chapter aims to develop strategies for providing psychiatric care to survivors and their families, in the aftermath of a pandemic outbreak. Lastly, special considerations in the application of psychopharmacological interventions are reviewed.

positive: Posttraumatic stress disorder and depression of survivors 12 months after the outbreak of Middle East respiratory syndrome in South Korea BACKGROUND: The 2015 outbreak of Middle East Respiratory Syndrome (MERS) in the Republic of Korea is a recent and representative occurrence of nationwide outbreaks of Emerging Infectious Diseases (EIDs). In addition to physical symptoms, posttraumatic stress disorder (PTSD) and depression are common following outbreaks of EID. METHODS: The present study investigated the long-term mental health outcomes and related risk factors in survivors of MERS. A prospective nationwide cohort study was conducted 12 months after the MERS outbreak at multi-centers throughout Korea. PTSD and depression as the main mental health outcomes were assessed with the Impact of Event Scale-Revised Korean version (IES-R-K) and the Patient Health Questionnaire-9 (PHQ-9) respectively. RESULTS: 42.9% of survivors reported PTSD (IES-R-K ≥ 25) and 27.0% reported depression (PHQ-9 ≥ 10) at 12 months post-MERS. A multivariate analysis revealed that anxiety (adjusted odds ratio [aOR], 5.76; 95%CI, 1.29–25.58; P = 0.021), and a greater recognition of stigma (aOR, 11.09, 95%CI, 2.28–53.90; P = 0.003) during the MERS-affected period were independent predictors of PTSD at 12 months after the MERS outbreak. Having a family member who died from MERS predicted the development of depression (aOR, 12.08, 95%CI, 1.47–99.19; P = 0.020). CONCLUSION: This finding implies that psychosocial factors, particularly during the outbreak phase, influenced the mental health of patients over a long-term period. Mental health support among the infected subjects and efforts to reduce stigma may improve recovery from psychological distress in an EID outbreak.

positive: COVID-19 and Liver. The current pandemic coronavirus labelled as Severe Acute Respiratory Distress Syndrome Coronavirus -2 (SARS -CoV-2) is a significant public health threat over for past few weeks. Overall case fatality rates range between 2-6%; however, the rates are higher in patients with severe disease, advanced age and underlying comorbidities like diabetes, hypertension and heart disease. Recent reports showed about 2-11% of patients with COVID-19 had underlying chronic liver disease. Experience from previous SARS epidemic suggest that 60% of patients developed various degrees of liver damage. In the current pandemic, hepatic dysfunction was seen in 14-53% of patients with COVID-19, particularly in those with severe disease. Cases of acute liver injury have been reported, associated with higher mortality. Hepatic involvement in COVID-19 could be multifactorial related to any of direct cytopathic effect of the virus, uncontrolled immune reaction, sepsis or drug induced liver injury. The postulated mechanism of viral entry is through the host ACE2 receptors that are abundantly present in type 2 alveolar cells. Interestingly, the expression of ACE2 receptors were identified in the gastrointestinal tract, vascular endothelium and cholangiocytes of the liver. Liver transplant recipients with COVID-19 have been reported recently. Effects of COVID-19 on underlying chronic liver disease requires a detailed evaluation and currently data is lacking and further research is warranted in this area. With lack of definitive therapy, patient education, hand hygiene and social distancing appears to be the cornerstone in minimising the disease spread.

positive: Re: Novel Coronavirus COVID-19 in late pregnancy: Outcomes of first nine cases in an inner city London hospital

positive: Quality of life and psychological status in survivors of severe acute respiratory syndrome at 3 months postdischarge Abstract Background Little is known about the long-term consequence of severe acute respiratory syndrome (SARS). We carried out an assessment on SARS patients after their recovery from their acute illness. Method Postal survey comprising Health-Related Quality of Life (HRQoL) questionnaires and anxiety and depression measures was sent to them at 3 months' postdischarge. Results There was a significant impairment in both the HRQoL and mental functioning. Forty-one percent had scores indicative of a posttraumatic stress disorder (PTSD); about 30% had likely anxiety and depression. Conclusion SARS has significant impact on HRQoL and psychological status at 3 months.

positive: Persisting olfactory dysfunction in patients after recovering from COVID-19

positive: La réhabilitation: indispensable pour les survivants d'un COVID-19 sévère./ [Rehabilitation is crucial for severe COVID-19 survivors] COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.

positive: The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals The global outbreak of coronavirus disease 2019 has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, postacute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular, and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with coronavirus disease 2019. Clinicians across the nation's rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings, and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands and the strategies to meet the needs of this population. The complications from coronavirus disease 2019 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting and at home through ongoing therapy either in-person or via telehealth.

positive: The COVID-19 pandemic: Important considerations for contact lens practitioners A novel coronavirus (CoV), the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), results in the coronavirus disease 2019 (COVID-19). As information concerning the COVID-19 disease continues to evolve, patients look to their eye care practitioners for accurate eye health guidance. There is currently no evidence to suggest an increased risk of contracting COVID-19 through contact lens (CL) wear compared to spectacle lens wear and no scientific evidence that wearing standard prescription spectacles provides protection against COVID-19 or other viral transmissions. During the pandemic there will potentially be significant changes in access to local eyecare. Thus, it is imperative CL wearers are reminded of the steps they should follow to minimise their risk of complications, to reduce their need to leave isolation and seek care. Management of adverse events should be retained within optometric systems if possible, to minimise the impact on the wider healthcare service, which will be stretched. Optimal CL care behaviours should be the same as those under normal circumstances, which include appropriate hand washing (thoroughly with soap and water) and drying (with paper towels) before both CL application and removal. Daily CL cleaning and correct case care for reusable CL should be followed according to appropriate guidelines, and CL exposure to water must be avoided. Where the availability of local clinical care is restricted, practitioners should consider advising patients to reduce or eliminate sleeping in their CL (where patients have the appropriate knowledge about correct daily care and access to suitable lens-care products) or consider the option of moving patients to daily disposable lenses (where patients have appropriate lens supplies available). Patients should also avoid touching their face, including their eyes, nose and mouth, with unwashed hands and avoid CL wear altogether if unwell (particularly with any cold or flu-like symptoms).

positive: SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standard for discharge Abstract An outbreak of COVID-19 in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With the active efforts from prevention and control, the quantity of discharged patients is escalating. How to manage these patients normatively is still challenging. We hereby reported an asymptomatic discharged patient with COVID-19 who was retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standard of COVID-19.

positive: Report of a series of healthy term newborns from convalescent mothers with COVID-19 BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable virus associated with a significantly increased risk of complications among the infected population. Few data are available for the outcome of pregnancy complicated by serious respiratory disease due to SARS-CoV-2 infection. AIM: We herein report a series of four neonates whose mothers had recovered from new coronavirus 2019 disease (COVID-19) diagnosed in the third trimester of pregnancy. METHODS: pregnant women with documented COVID-19 infection during their pregnancy, who gave birth in Parma Hospital, University of Parma, Italy, in March and April 2020, during the peak of incidence of COVID-19 in Italy. Clinical records and laboratory tests were retrospectively reviewed. RESULTS: All neonates were delivered at term in good conditions without congenital COVID-19 infection. CONCLUSIONS: Findings from our series of cases indicated that adverse effects on foetuses from pregnancies complicated by COVID-19 infection in late pregnancy are unlikely.

positive: WITHDRAWN: Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge

positive: SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge An outbreak of coronavirus disease (COVID-19) in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With active efforts of prevention and control, more and more patients are being discharged. However, how to manage these patients normatively is still challenging. This paper reports an asymptomatic discharged patient with COVID-19 who retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standards of COVID-19.

positive: The effect of massage on the quality of life in patients recovering from COVID-19: A systematic review protocol BACKGROUND: There is a worldwide outbreak of covid-19, and as the number of patients increases, more and more patients are recovering. Massage is used as an alternative therapy. Currently, there are no relevant articles for systematic review. METHODS: We will search the randomized controlled trials related to acupuncture therapy and postoperative anorectal diseases from inception to January 2020. The following database is our focus area: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-Fang Database. All published randomized controlled trials in English or Chinese related to massage for COVID-19 will be included. Primary outcome asthe influence of massage on the quality of life of convalescent patients. Secondary outcomes were accompanying symptoms (such as myalgia, expectoration, stuffiness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappear rate, negative COVID-19 results rate on 2 consecutive occasions (not on the same day), average hospitalization time, clinical curative effect, and improved quality of life. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether massage is an effective intervention on the quality of life in patients recovering. PROSPERO REGISTRATION NUMBER: CRD42020181398

positive: Novel Coronavirus Pneumonia (COVID-19) Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section CT Features During Recovery BACKGROUND: To retrospectively analyze the evolution of clinical features and thin-section CT imaging of novel coronavirus pneumonia (COVID-19) in 17 discharged patients. METHODS: Serial thin-section CT scans of 17 discharged patients with COVID-19 were obtained during recovery. Longitudinal changes of clinical parameters and CT pattern were documented in all patients during 4 weeks since admission. CT score was used to evaluate the extent of the disease. RESULTS: There was a marked improvement of fever, lymphocytes count, C-reactive protein and erythrocyte sedimentation rate within the first two weeks since admission. However, the mean CT score rapidly increased from the 1(st) to 3(rd) week, with a top score of 8.2 obtained in the 2(nd) week. During the 1(st) week, the main CT pattern was ground-glass opacities (GGO,76.5%). The frequency of GGO (52.9%) decreased in the 2(nd) week. Consolidation and mixed patterns (47.0%) were noted in the 2(nd) week. Thereafter, consolidations generally dissipated into GGO and the frequency of GGO increased in the 3(rd) week (76.5%) and 4(th) week (71.4%). Opacities were mainly located in the peripheral (76.5%), subpleural (47.1%) zones of the lungs, and presented as focal (35.3%) or multifocal (29.4%) in the 1(st) week and became more diffuse in the 2(nd) (47.1%) and 3(rd )week (58.8%), then showed reduced extent in 4(th )week (50%). CONCLUSIONS: The progression course of CT pattern was later than the clinical parameters within the first two weeks since admission; however, there was a synchronized improvement in both clinical and radiologic features in the 4(th) week.

positive: COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – also known as COVID-19 – is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.

positive: Challenges in the management of older patients with acute coronary syndromes in the COVID-19 pandemic Ischaemic heart disease (IHD), in particular acute coronary syndrome (ACS), comprising ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina, is the leading cause of death worldwide. Age is a major predictor of adverse outcome following ACS. COVID-19 infection seems to escalate the risk in older patients with heart disease. Increasing odds of in-hospital death is associated with older age following COVID-19 infection. Importantly, it seems older patients with comorbidities such as cardiovascular disease (CVD), in particular IHD, diabetes and hypertension, are at the highest risk of mortality following COVID-19 infection. The evidence is sparse on the optimal care of older patients with ACS with lack of robust randomised controlled trials. In this setting, with the serious threat imposed by the COVID-19 pandemic in the context of rapidly evolving knowledge with much unknown, it is important to weigh the risks and benefits of treatment strategies offered to older patients. In cases where risks outweigh the benefits, it might not be an unreasonable option to treat such patients with a conservative or a palliative approach. Further evidence to elucidate whether invasive management is beneficial in older patients with ACS is required out-with the COVID-19 pandemic. Though it is hoped that the actual acute phase of COVID-19 infection will be short lived, it is vital that important clinical research is continued, given the long-term benefits of ongoing clinical research for patients with long-term conditions, including CVD. This review aimed to evaluate the challenges and the management strategies in the care of older patients presenting with ACS in the context of the COVID-19 pandemic.

positive: Severe Immune Thrombocytopenia Complicated by Intracerebral Haemorrhage Associated with Coronavirus Infection: A Case Report and Literature Review Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that causes isolated thrombocytopenia. Many viruses have been identified as triggering the autoimmune process, including HIV, MCV, EBV, parvovirus, rubella and measles. However, ITP in association with coronavirus infection has not previously been reported. We describe the case of a healthy man who presented with severe ITP complicated by intracranial haemorrhage following upper respiratory tract infection. An infection screen revealed coronavirus infection. LEARNING POINTS: Coronavirus can cause severe immune thrombocytopenic purpura (ITP). Intracerebral haemorrhage is an uncommon presentation of ITP. Intravenous immunoglobulin and steroids are very effective treatments for severe ITP.

positive: The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.

positive: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

positive: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m(2); with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA(1c), diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

positive: Retest positive for SARS‐CoV‐2 RNA of “recovered” patients with COVID‐19: Persistence, sampling issues, or re‐infection? “Retest Positive” for severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2) from “recovered” coronavirus disease‐19 (COVID‐19) has been reported and raised several important questions for this novel coronavirus and COVID‐19 disease. In this commentary, we discussed several questions: (a) Can SARS‐CoV‐2 re‐infect the individuals who recovered from COVID‐19? This question is also associated with other questions: whether or not SARS‐CoV‐2 infection induces protective reaction or neutralized antibody? Will SARS‐CoV‐2 vaccines work? (b) Why could some recovered patients with COVID‐19 be re‐tested positive for SARS‐CoV‐2 RNA? (c) Are some recovered pwith atients COVID‐19 with re‐testing positive for SARS‐CoV‐2 RNA infectious? and (d) How should the COVID‐19 patients with retest positive for SARS‐CoV‐2 be managed?

positive: Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions

positive: Rehab facilities face COVID-19 crunch as more patients recover.

positive: Coronaviruses and the cardiovascular system: acute and long-term implications ;European Heart Journal ;Oxford Academic The recent outbreak of coronavirus disease 2019 (COVID-19) provides a further challenge in the battle against outbreaks of novel virus infections and has been declared a public health emergency of international concern Much has been learnt in the course of preceding epidemics, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and H1N1 influenza, and it is now recognized that their overall health burden may be under-estimated since extra-pulmonary manifestations are frequent 1 Acute and chronic cardiovascular complications of pneumonia are common and result from various mechanisms, including relative ischaemia, systemic inflammation, and pathogen-mediated damage There is, however, only limited published data concerning cardiovascular presentations in the wake of viral epidemics The present COVID-19 outbreak emphasizes the need for greater awareness of the immediate and long-term cardiovascular implications of viral infection and the significant gaps in knowledge that future research will need to address

positive: Critical Complications of COVID-19: A systematic Review and Meta-Analysis study Background: Coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has spread worldwide in a short period and caused a pandemic. The goal of this meta-analysis is to evaluate the prevalence of most common symptoms and complications of COVID-19. Methods: All related studies assessing the clinical complications of COVID-19 have been identified through web search databases (PubMed and Scopus). Relevant data were extracted from these studies and analyzed by stata (ver 14) random-effects model. The heterogeneity of studies were assessed by I2 index. The publication bias was examined by Funnel plots and Eggers test. Results: 30 studies were in our meta-analysis including 6 389 infected patients. The prevalence of most common symptoms were: fever 84.30% (95% CI: 77.13-90.37; I2=97.74%), cough 63.01% (95% CI: 57.63-68.23; I2=93.73%), dyspnea 37.16% (95% CI: 27.31-47.57%; I2=98.32%), fatigue 34.22% (95% CI: 26.29-42.62; I2=97.29%) and diarrhea 11.47 %(95% CI: 6.96-16.87; I2=95.58%), respectively. The most prevalent complications were acute respiratory distress syndrome (ARDS) 33.15% (95% CI: 23.35-43.73; I2=98.56%), acute cardiac injury 13.77% (95% CI: 9.66-18.45; I2=91.36%), arrhythmia 16.64% (95% CI: 9.34-25.5; I2=92.29%), heart failure 11.50% (95% CI: 3.45-22.83; I2=89.48%), and acute kidney injury (AKI) 8.40 %(95% CI: 5.15-12.31; I2=95.22%, respectively. According to our analysis, mortality rate of COVID-19 patients were 12.29% (95% CI: 6.20-19.99; I2=98.29%). Conclusion: We assessed the prevalence of the main clinical complications of COVID-19 and found that after respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

positive: Prevalence and Recovery From Olfactory and Gustatory Dysfunctions in Covid-19 Infection: A Prospective Multicenter Study BACKGROUND: Covid-19 is defined by an association of multiple symptoms, including frequently reported olfactory and gustatory disorders. OBJECTIVE: The main purpose of this study was to analyze the prevalence of these neurosensory impairments in patients with Covid-19, and to assess short-term recovery. METHODS: We performed a multicenter case series study during the Covid-19 epidemic. All patients presenting a RT-PCR-confirmed SARS-CoV-2 infection were included, whether hospitalized or treated at home. To analyze the prevalence and features of olfactory and gustatory dysfunctions, a phone interview was conducted 5 days after the positive PCR result. The questionnaire was submitted again 10 days later to patients having reported olfactory and gustatory disorders, in order to assess their recovery. RESULTS: 115 patients were included in our study. 81 patients (70%) reported olfactory and gustatory disorders without nasal obstruction or rhinorrhea. These impairments were more frequently reported in the female population, young people, and house-bound patients with mild symptomatic forms. Short-term recovery assessed at Day 15 was complete for 64% of the patients, and incomplete in 33%. Median recovery time was 15 days (4-27 days) after olfactory or gustatory symptom onset. CONCLUSION: Olfactory and gustatory dysfunctions related to Covid-19 are frequently reported and prevalent in mild symptomatic forms of the disease. Recovery in most cases seems rapid and complete.

positive: Comment on “Hearing loss and COVID-19: A note”

positive: Recovering from COVID-19: the key issues

positive: The impact of nutrition on COVID-19 susceptibility and long-term consequences While all groups are affected by the COVID-19 pandemic, the elderly, underrepresented minorities, and those with underlying medical conditions are at the greatest risk. The high rate of consumption of diets high in saturated fats, sugars, and refined carbohydrates (collectively called Western diet, WD) worldwide, contribute to the prevalence of obesity and type 2 diabetes, and could place these populations at an increased risk for severe COVID-19 pathology and mortality. WD consumption activates the innate immune system and impairs adaptive immunity, leading to chronic inflammation and impaired host defense against viruses. Furthermore, peripheral inflammation caused by COVID-19 may have long-term consequences in those that recover, leading to chronic medical conditions such as dementia and neurodegenerative disease, likely through neuroinflammatory mechanisms that can be compounded by an unhealthy diet. Thus, now more than ever, wider access to healthy foods should be a top priority and individuals should be mindful of healthy eating habits to reduce susceptibility to and long-term complications from COVID-19.

positive: Years of life lost due to the psychosocial consequences of COVID19 mitigation strategies based on Swiss data Background: The pandemic caused by COVID-19 has forced governments to implement strict social mitigation strategies to reduce the acute morbidity and mortality from acute infections. These strategies however carry a significant risk for mental health which can lead to increased short-term and long-term mortality, which is currently not included in modelling the impact of the pandemic. Methods: We used years of life lost (YLL) as the main outcome measure as applied to Switzerland as an exemplar. We focused on suicide, depression, alcohol use disorder, childhood physical abuse and social isolation as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We also estimated a minimum duration of mitigation of 3 months based on current public health plans. Results: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by a subpopulation of 2.1 percent of the population, the average of whom suffer an average 9.79 YLL. Conclusions: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, model like the one presented here highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

positive: Covid-19: accelerating recovery Covid-19 infections and related illness and death are rightly at the forefront of our minds. It is critical that we consider how to reduce infections, treat those who are ill and protect health systems. We must, however, also consider how the pandemic is affecting the families of those infected, and how interventions to prevent the spread of the virus come with large negative economic and social consequences. We must begin to identify the ways in which we can soften these blows and recover from the negative consequences over the medium and long-term. We highlight here the importance of moving away the tendency to search for interventions to improve one outcome at a time. It will be essential, particularly in highly resource constrained settings, to look for accelerators, interventions which improve multiple outcomes simultaneously. We discuss how this will be especially important for groups who are at particular risk at this time, including of long-term negative outcomes. These include very young children, adolescents and those who have limited capacity to benefit from narrow interventions given critical needs in multiple domains. Searching for accelerators requires that we take a step back and look to identify common causes of negative outcomes and consider how we might address them. For many countries, recovery from this epidemic will be highly constrained by the limited availability of financial resources. Wise investments will be especially important at this time.

positive: Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis. OBJECTIVE To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months, and beyond. DATA SYNTHESIS Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15-45%); and reduced exercise capacity ((mean 6-min walking distance 461 m, CI 450-473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31-47%), depression (33%, 95% CI 20-50%) and anxiety (30%, 95% CI 10-61) beyond 6 months were considerable. Low scores on Short-Form 36 were identified at 6 months and beyond. CONCLUSION Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.

positive: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of "post-COVID-19 Cardiac Syndrome".

positive: Anxiety persists after recovery from acquired COVID-19 in anaesthesiologists

positive: LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.

positive: [Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures]. The Corona Virus Disease 2019 (COVID-19) outbroke in Wuhan, China in December 2019 and the severe acute respiratory syndrome (SARS) outbroke in Guangzhou, China in 2003 were caused by highly pathogenic coronaviruses with high homology. Since the 2019 novel coronavirus has strong transmissibility and progress rapidly. It has caused negative social effects and massive economic damage on a global scale. While there is currently no vaccine or effective drugs. Pulmonary fibrosis is a pulmonary disease with progressive fibrosis, which is the main factor leading to pulmonary dysfunction and quality of life decline in SARS survivors after recovery. Extensive epidemiological, viral immunological, and current clinical evidences support the possibility that pulmonary fibrosis may be one of the major complications in COVID-19 patients. Although there are no reports on the mechanism of COVID-19 inducing pulmonary fibrosis, based on the existing theoretical basis, we focus on the possible mechanism of COVID-19 sustained lung damaging, the key role of abnormal immune mechanism in the initiation and promotion of pulmonary fibrosis, and the corresponding therapeutic measures.

positive: Clinical analysis of 2019 coronavirus disease (COVID-19) on one case with living-related kidney transplantation/ 中华器官移植杂志 Objective@#To analyze the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease (COVID-19) .@*Method@#The clinical diagnosis and treatment of one relative renal transplant recipient after the occurrence of COVID-19 were analyzed retrospectively, including the course of onset, clinical manifestations, blood routine test, renal function, lung CT scan, nucleic acid detection, outpatient and inpatient therapies and outcomes.@*Result@#The case was diagnosed as COVID-19 (severe type) with influenza A virus infection. The clinical symptoms were gradually relieved and the lung lesions were absorbed through the treatment of reduce and stop taking immunosuppressant, antiviral therapy of abidol/oseltamivir, prevention of bacterial infection, hormone anti-inflammatory, oxygen inhalation, nutritional support and adequate rest.@*Conclusion@#This case present typical characteristics of COVID-19 in epidemiological investigation, clinical manifestation, examination, pulmonary imaging and etiology. After comprehensive treatment including reduce and stop immunosuppressive therapy, clinical cure was achieved. The long-term effect of COVID-19 on this immunosuppressive patient remains follow-up.

positive: Prevalence and Recovery From Olfactory and Gustatory Dysfunctions in Covid-19 Infection: A Prospective Multicenter Study. BACKGROUND Covid-19 is defined by an association of multiple symptoms, including frequently reported olfactory and gustatory disorders. OBJECTIVE The main purpose of this study was to analyze the prevalence of these neurosensory impairments in patients with Covid-19, and to assess short-term recovery. METHODS We performed a multicenter case series study during the Covid-19 epidemic. All patients presenting a RT-PCR-confirmed SARS-CoV-2 infection were included, whether hospitalized or treated at home. To analyze the prevalence and features of olfactory and gustatory dysfunctions, a phone interview was conducted 5 days after the positive PCR result. The questionnaire was submitted again 10 days later to patients having reported olfactory and gustatory disorders, in order to assess their recovery. RESULTS 115 patients were included in our study. 81 patients (70%) reported olfactory and gustatory disorders without nasal obstruction or rhinorrhea. These impairments were more frequently reported in the female population, young people, and house-bound patients with mild symptomatic forms. Short-term recovery assessed at Day 15 was complete for 64% of the patients, and incomplete in 33%. Median recovery time was 15 days (4-27 days) after olfactory or gustatory symptom onset. CONCLUSION Olfactory and gustatory dysfunctions related to Covid-19 are frequently reported and prevalent in mild symptomatic forms of the disease. Recovery in most cases seems rapid and complete.

positive: Recovery from the coronavirus disease-2019 (COVID-19) in two patients with coexisted (HIV) infection

positive: Recovery rate and factors associated with smell and taste disruption in patients with coronavirus disease 2019 PURPOSE: To determine the occurrence of olfactory and gustatory disruptions in COVID-19 patients, their association with demographic and clinical features and prognosis. MATERIAL AND METHODS: This observational cohort study involved consecutively diagnosed COVID-19 patients tested between March the 3rd 2020 and March the 24th 2020, in a geographically defined cohort area. All COVID-19 patients were evaluated in a University Hospital. The primary outcome of interest is the prevalence of smell and taste alterations, factors associated and recovery rate. Univariate and multivariate analysis by logistic regression was performed to detect factors associated to these symptoms. RESULTS: 151 patients were included and 99 (65.3%) reported olfactory or gustatory symptoms. Olfactory dysfunction was reported by 75 patients (49.7%). Isolated anosmia was found in 2 patients (1.3%). Gustatory dysfunction was reported by 91 patients (60.3%). Factors associated with higher prevalence of smell dysfunction included age, sex, and comorbidities. The time to smell disruption development was significantly shorter in mild to moderate patients than in severe patients (p = 0.043). In 85.3% of patients with smell disruption, the symptom had been resolved in the first 2 months. 14.7% of patients remained symptomatic after 3 months of follow-up. CONCLUSIONS: Olfactory and gustatory dysfunction was common in COVID-19 patients. Smell disruption has high recovery rate and was associated with age, sex, and clinical severity. It may be beneficial to investigate the appearance of taste and/or smell disruptions in individual patients, with respect to diagnosis and prognosis.

positive: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19 INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory dysfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1st, 2020. Participants were posteriorly asked by e-mail to verify data on the recovery of sudden olfactory loss and test for COVID-19 at the end of the data collection period. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p=0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p=0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p=0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p=0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.

positive: The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

positive: Immediate and long-term consequences of COVID-19 infections for the development of neurological disease Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.

positive: Predictive Data Mining Models for Novel Coronavirus (COVID-19) Infected Patients’ Recovery Novel coronavirus (COVID-19 or 2019-nCoV) pandemic has neither clinically proven vaccine nor drugs; however, its patients are recovering with the aid of antibiotic medications, anti-viral drugs, and chloroquine as well as vitamin C supplementation. It is now evident that the world needs a speedy and quicker solution to contain and tackle the further spread of COVID-19 across the world with the aid of non-clinical approaches such as data mining approaches, augmented intelligence and other artificial intelligence techniques so as to mitigate the huge burden on the healthcare system while providing the best possible means for patients' diagnosis and prognosis of the 2019-nCoV pandemic effectively. In this study, data mining models were developed for the prediction of COVID-19 infected patients’ recovery using epidemiological dataset of COVID-19 patients of South Korea. The decision tree, support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor algorithms were applied directly on the dataset using python programming language to develop the models. The model predicted a minimum and maximum number of days for COVID-19 patients to recover from the virus, the age group of patients who are of high risk not to recover from the COVID-19 pandemic, those who are likely to recover and those who might be likely to recover quickly from COVID-19 pandemic. The results of the present study have shown that the model developed with decision tree data mining algorithm is more efficient to predict the possibility of recovery of the infected patients from COVID-19 pandemic with the overall accuracy of 99.85% which stands to be the best model developed among the models developed with other algorithms including support vector machine, naive Bayes, logistic regression, random forest, and K-nearest neighbor.

positive: HOW TO DETECT AND TRACK CHRONIC NEUROLOGIC SEQUELAE OF COVID-19? USE OF AUDITORY BRAINSTEM RESPONSES AND NEUROIMAGING FOR LONG-TERM PATIENT FOLLOW-UP. This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.

positive: Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals. Based on different categories of disease severity (asymptomatic, regional/systemic symptoms, hospitalisation, myocardial damage, and/or myocarditis), in this point-of-view article we offer the (sports) cardiologist or sports physician in the Netherlands a practical guide to pre-participation screening, and diagnostic and management strategies in all athletes >16 years of age after COVID-19 infection.

positive: Clinical Course, Imaging Features, and Outcomes of COVID-19 in Kidney Transplant Recipients Coronavirus disease 2019 (COVID-19) is a novel and highly contagious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older adults and patients with comorbidities and immunosuppressive conditions may experience severe signs and symptoms that can lead to death. This case series assesses the clinical course, imaging features, and outcomes for 12 patients with COVID-19 and a history of kidney transplantation. Patients were evaluated for symptoms, laboratory data, imaging findings, and outcomes from February 2020 to April 2020. Fever, cough, and dyspnea were the most common clinical symptoms, noted in 75% (nine/12), 75% (nine/12), and 41.7% (five/12) of the patients, respectively. Most of the patients had a normal white blood cell count, while 33.3% (four/12) had leukopenia and 8.3% (one/12) had leukocytosis. A combination of consolidation and ground glass opacity was the most predominant (75%) pattern of lung involvement on computed tomography (CT). Eight patients died of severe COVID-19 pneumonia and acute respiratory distress syndrome and four were discharged. All recovered cases had a unilateral peripheral pattern of involvement limited to only one zone on initial chest CT. It seems that CT imaging has an important role in predicting COVID-19 outcomes for solid organ transplant recipients. Future studies with long-term follow up and more cases are needed to elucidate COVID-19 diagnosis, outcome, and management strategies for these patients.

positive: Recessions and health: The long‐term health consequences of responses to the coronavirus The lockdown measures that were implemented in the spring of 2020 to stop the spread of Covid‐19 are having a huge impact on economies in the UK and around the world. In addition to the direct impact of Covid‐19 on health, the following recession will have an impact on people's health outcomes. This paper reviews economic literature on the longer run health impacts of business cycle fluctuations and recessions. Previous studies show that an economic downturn, which affects people through increased unemployment, lower incomes and increased uncertainty, will have significant consequences on people's health outcomes both in the short and longer term. The health effects caused by these adverse macroeconomic conditions will be complex, and will differ across generations, regions and socioeconomic groups. Groups that are vulnerable to poor health are likely to be hit hardest even if the crisis hit all individuals equally, and we already see that some groups such as young workers and women are worse hit by the recession than others. Government policies during and after the pandemic will play an important role in determining the eventual health consequences. This article is protected by copyright. All rights reserved

positive: Nervous system damage after COVID-19 infection: presence or absence?

positive: An overview of COVID-19 Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

positive: Covid-19: adverse mental health outcomes for healthcare workers.

positive: Incidence of thrombotic complications in critically ill ICU patients with COVID-19 Abstract Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

positive: Neurological manifestations and complications of COVID-19: A Literature Review Abstract The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2109 and rapidly spread to more than 200 countries as a global health pandemic. There are more than 2.3 million confirmed cases and around 165,000 fatalities. The primary manifestation is respiratory and cardiac but neurological features are also being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

positive: Long term complications and rehabilitation of COVID-19 patients With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.

positive: Mental Health Consequences during the Initial Stage of the 2020 Coronavirus Pandemic (COVID-19) in Spain The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.

positive: Thin-Section Computed Tomography Manifestations During Convalescence and Long-Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS) BACKGROUND: SARS is not only an acute disease, but also leads to long-term impaired lung diffusing capacity in some survivors. However, there is a paucity of data regarding long-term CT findings in survivors after SARS. The aim of this study was to assess the changes in lung function and lung thin-section computed tomography (CT) features in patients recovering from severe acute respiratory syndrome (SARS), especially the dynamic changes in ground-glass opacity (GGO). MATERIAL/METHODS: Clinical and radiological data from 11 patients with SARS were collected. The serial follow-up thin-section CTs were evaluated at 3, 6, and 84 months after SARS presentation. The distribution and predominant thin-section CT findings of lesions were evaluated. RESULTS: The extent of the lesions on the CT scans of the 11 patients decreased at 6 and 84 months compared to 3 months. The number of segments involved on 84-month follow-up CTs was less than those at 6 months (P<0.05). The predominant thin-section CT manifestation at 84 months (intralobular and interlobular septal thickening) was different than that at 6 months, at which GGO was predominant. CONCLUSIONS: During convalescence after SARS, GGO and intralobular and interlobular septal thickening were the main thin-section CT manifestation. Intralobular and interlobular septal thickening predominated over GGO at 84 months.

positive: Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.

positive: Characteristics, Treatment Outcomes and Role of Hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study. Purpose The present study was undertaken to investigate epidemiological distribution, clinical manifestation, co morbid status, treatment strategy and case fatality index of emerging COVID-19 infection at SMS Medical College Hospital, Jaipur, Rajasthan. It also evaluated efficacy of hydroxychloroquine (HCQ) in treatment of patients and risk of serious adverse outcomes in patients with COVID-19 in relation to their co morbid status. Materials and methods In an attempt to provide extensive information pertaining to epidemiological and clinical characteristics of COVID-19, the present study was undertaken on 522 patients. The patients were COVID-19 confirmed positive by genomic analysis through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at SMS Medical College and Attached Hospitals, Jaipur. The indoor admitted patient's information inclusive of demographic profile (age, sex, nationality, residence), date of confirmation for positive COVID-19 case, travel/ exposure history, date of recovery/ death, clinical features, co morbidities and treatment plan was recorded. A serial follow-up of recovered patients to evaluate infective period of the disease was also part of the study. Results A total of 522 patients of laboratory confirmed COVID-19 test by RT-PCR at SMS Hospitals, Jaipur were assessed. Among the confirmed cases, most of patients were young adult in the age group with mean age of 35.42 years. 22.41% patients were below 20 years of age, majority of patients (58.80%) were in the age range of 21 to 50 years and only 18.79% patient population was in the age range of above 50 years. Females (39.08%) were affected less than males (60.91%) with an average sex ratio of female: male being 0.64. Out of the total analyzed patients, only 24.32% patients were symptomatic, among them fever (55.90%), cough (52.75%), sore throat (49.60%) and shortness of breath (46.45%) were the most common presenting clinical manifestations while a few patients also had symptoms of headache (26.77%), chest pain (6.29%) and other symptoms (7.87%) like pain abdomen, fatigue, joints pain, altered sensorium etc. Most of symptomatic patients belonging to older age group. An average of 40.40% patient population of above 50 years of age, were symptomatic while none of the patients below 10 years of age were symptomatic. 13.98% patients had some or the other underlying co morbid disease. The most prevalent co morbidity was hypertension (42.46%) followed by Diabetes mellitus (39.72%), Old k-chest (20.54%), COPD/ Bronchial Asthma (16.43%), Coronary artery disease (13.69%), Chronic kidney disease (13.69%) and Valvular heart disease (6.84%) distributed in co morbid patients of COVID-19. 60.27% of patient population with underlying co morbid conditions were more prone to develop symptomatology complex as compared to that observed in patients with no co morbidity (18.42%). 116 patients had recovered with effective treatment till the date of data analysis. Time of recovery was counted from the date of positive report to 1st negative report of oropharyngeal sample by RT-PCR for COVID-19 with an average recovery time of 8.15 days. 23.27% patients recovered within 5 days, while 52.58% patients took about 6-10 days, 23.27% patients took 11-15 days and remaining 0.86% took more than 16 days to recover. In the present study 15 patients had died till analysis of data, among the deceased, 73.33% were above 50 year of age with a male preponderance (66.6%). Interestingly, all deceased (100%) had presented with clinical manifestations of COVID-19 and all had underlying multiple co morbid conditions. Majority of patients had early mortality after admission to hospital with two third death account in initial three days. Asymptomatic patients (cases) treated with HCQ recovered early (average recovery time =5.4 days) compared to asymptomatic patients who did not receive any treatment (control group) and had longer recovery time (average recovery time =7.6 days). Conclusion The varied spectra of COVID-19 mostly affects young adult age group (third to fifth decades of life). Interestingly, early age group was also affected in significant proportion when compared with similar data from other countries. It was observed that male population seemed to be was more prone to getting infected. Majority of COVID-19 positive patients (nearly three-fourth) were asymptomatic (mostly in young age range) at the time of diagnosis, which poses a major challenge for health care workers. Fever, cough, sore throat and shortness of breath were major symptoms that could be detected in such COVID-19 patients. Symptomatic clinical manifestations were more common in old age population. Infectivity was higher in patients that had underlying co morbid disease, especially in patients with multiple co morbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease. Average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and co morbid patients as compared to other similarly matched group. Most of mortality was noted within first few days of admission, suggestive of early mortality due to the primary disease process. Treatment with HCQ had early recovery without effectively influencing the overall mortality.

positive: Failure of early extubation among cases of coronavirus disease-19 respiratory failure: Case report and clinical experience RATIONALE: Extubation strategy for mechanically ventilated patients with Coronavirus Disease 19 is different from that for patients with other viral pneumonia. We reported 2 cases of Coronavirus Disease 19 receiving tracheal intubation twice during the hospitalization. PATIENT CONCERNS: Two elderly patients with onset of fever and upper respiratory tract infection were confirmed as Coronavirus Disease 19, 1 of whom had chronic obstructive pulmonary disease previously. With active antiviral and noninvasive respiratory supportive therapy, there was no improvement, thus mechanical ventilation (MV) was adopted. Combining with symptomatic and supportive treatment, their oxygenation recovered and then extubation was carried out. However, 96âhours later, they underwent endotracheal intubation again due to their Coronavirus Disease 19 progression. DIAGNOSIS: Critically ill Coronavirus Disease 19 requiring tracheal intubation owing to respiratory failure with lung.javascript. INTERVENTIONS: Initial Strategy for respiratory failure included endotracheal intubation, MV, antiviral treatment and cortisol in both cases. When extubation criteria were satisfied, early discontinuation of MV was conducted, then rehabilitation exercise and nutritional support followed. However, 96âhours later, the disease progressed leading to respiratory failure again, thus reintubation was performed. Later, veno-venous extracorporeal membrane oxygenation was performed owing to aggravation of respiratory failure, assisted by prone position treatment and sputum drainage, then status became stable and stepped into recovery stage. OUTCOMES: Both patients underwent reintubation, and their MV time and Intensive care unit residence time were prolonged. Through prone position treatment, sputum drainage and awake extracorporeal membrane oxygenation strategy, patient has been transferred to rehabilitation unit in Case 1, and patient in Case 2 has been in recovery stage as well with stable pulmonary status and was expected to receive evaluation in recent future. LESSONS: Course of Coronavirus Disease 19 is relatively longer, and failure rate of simple early extubation seemes higher. To reduce the likelihood of reintubation and iatrogenic injury, individualized assessment is recommended.

positive: Subjective smell and taste changes during the COVID-19 pandemic: Short term recovery Since the COVID-19 pandemic began, many individuals have reported acute loss of smell and taste. In order to better characterize all patients with these symptoms, a longitudinal national survey was created. Since April 10, 2020, 549 completed the initial survey, with 295 completing 14-day, and 202 completing 1-month follow up surveys. At 1-month follow-up, 67.1% reported a return to “very good” or “good” smell, and 73.1% reported a return to “very good” or “good” taste. Chemosensory changes are a cardinal sign of COVID-19. Fortunately, our data, representing a large longitudinal study of patients experiencing smell and taste losses during the COVID-19 pandemic, indicates that the majority appear to recover within a month.

positive: Reactivation of COVID‐19 – 14 days from the onset of symptoms may not be enough to allow dental treatment The pandemic of coronavirus disease 2019 (COVID‐19) has become a global health disaster (Phelan et al., 2020). On the level of dental practice, the risk of cross infection between infected patients and dental professionals is quite alarming. The current recommendations suggest that dental treatment of patients with suspected/confirmed coronavirus disease should be postponed for at least 14 days from the onset of symptoms (Peng et al., 2020).

positive: Impaired pulmonary function in discharged patients with COVID-19: More work ahead

positive: The competing risk between in-hospital mortality and recovery: A pitfall in COVID-19 survival analysis research Background Many studies investigating mortality and recovery in COVID-19 have been published recently. The majority of these studies used the standard Cox Proportional Hazards (Cox PH) model without taking into account the presence of competing risks. This study investigates, through extensive simulations, the bias in estimating the hazard ratio (HR) of death due to COVID-19 and the absolute risk reduction (ARR) when competing risks are not taken into consideration, and suggests an alternative method. Methods We simulated data for a fictive clinical trial in COVID-19 patients, to mimic recent trials involving the use of Hydroxychloroquine, Remdesivir, and convalescent plasma therapy for example. The primary outcome is the time from randomization until death due to COVID-19. Six scenarios representing different situations of the effect of treatment on death and its competing event recovery were considered. The HR of death and the 28-day ARR were estimated using the Cox PH model and the Fine and Gray (FG) model which takes competing risks into account. The estimates were then compared to their corresponding true values and the magnitude of misestimation quantified. Results The Cox PH model misestimated the true HR of death in the majority of the scenarios. The magnitude of this misestimation increased when the process of recovery was faster and/or the chance of recovery was higher. In some cases, this model has also incorrectly shown a harmful effect of treatment when it was in fact beneficial. The true 28-day ARR of death was also misestimated, and this misestimation increased in magnitude when the process of recovery was faster. The results obtained from the FG competing risks model are all consistent and show no misestimation or changes in direction for both the HR and the 28-day ARR of death. Conclusion There is a substantial risk of misleading results in COVID-19 research if recovery and death are not considered as competing risk events. We strongly suggest the use of a competing risk approach to re-analyze relevant published data that have used the Cox PH model.

positive: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.

positive: The COVID-19 rehabilitation pandemic(1) The coronavirus disease 2019 (COVID-19) pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.

positive: Potentially irreversible olfactory and gustatory impairments in COVID-19: indolent vs. fulminant SARS-CoV-2 neuroinfection

positive: [Rehabilitation is crucial for severe COVID-19 survivors]. COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.

positive: Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

positive: [Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures] The Corona Virus Disease 2019 (COVID-19) outbroke in Wuhan, China in December 2019 and the severe acute respiratory syndrome (SARS) outbroke in Guangzhou, China in 2003 were caused by highly pathogenic coronaviruses with high homology. Since the 2019 novel coronavirus has strong transmissibility and progress rapidly. It has caused negative social effects and massive economic damage on a global scale. While there is currently no vaccine or effective drugs. Pulmonary fibrosis is a pulmonary disease with progressive fibrosis, which is the main factor leading to pulmonary dysfunction and quality of life decline in SARS survivors after recovery. Extensive epidemiological, viral immunological, and current clinical evidences support the possibility that pulmonary fibrosis may be one of the major complications in COVID-19 patients. Although there are no reports on the mechanism of COVID-19 inducing pulmonary fibrosis, based on the existing theoretical basis, we focus on the possible mechanism of COVID-19 sustained lung damaging, the key role of abnormal immune mechanism in the initiation and promotion of pulmonary fibrosis, and the corresponding therapeutic measures.

positive: Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data BACKGROUND. The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS. We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS. The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS. The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

positive: COVID-19 pandemic and its recovery time of patients in India: A pilot study BACKGROUND AND AIMS: Covid-19 virus started from Wuhan, China and has brought the world down to its knees. It has catapulted as a venomous global phenomenon. This study focuses on the Covid-19 situation in India and its recovery time. METHOD: The study period is from March 1, 2020 to April 25, 2020. A random sample of 221 individuals found positive with Covid-19 from March 1, 2020 to 31st March is included in the study which is followed up April 25, 2020. There is a male preponderance in the sample with 66% of the Covid-19 patients being male and about 34% being female. Kaplan-Meier Product limit estimator, Kaplan-Meier survival curve and Log-rank test are used to analyze the recovery time of Covid-19 patients. RESULT: From the results of the study, it is found that the average recovery time of Covid-19 patients in India is 25 days (95% C.I. 16 days to 34 days). Only 4% of the patients get cured after 10 days of treatment. The recovery time of male and female patients is not statistically different. Recovery time of patients belonging to different age groups is also not statistically significant. CONCLUSION: This information on recovery time of Covid-19 patients will help planners to chalk out effective strategies.

positive: A Follow-up Study of Recovered Patients with COVID-19 in Wuhan, China

positive: Clinical Features and Short-term Outcomes of Elderly Patients With COVID-19 Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. Methods 204 elderly patients (≥60 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. Results Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414 to 3.517;p < 0.001), older age (HR 1.1, 95% CI 1.070 to 1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310 to 15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471 to 10.433; p = 0.006) were independently associated with death. Conclusion Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.

positive: Rehab facilities face COVID-19 crunch as more patients recover

positive: Leukopenia of Asymptomatic COVID-19 Infections under 18 Years Old in Recovery Stage Background In December, 2019, a type of novel coronavirus which was designated novel coronavirus 2019 (2019-nCoV) by World Health Organization (WHO) occurred in Wuhan, Hubei, China. The epidemiological and clinical characteristics of those patients under 18 years old in the recovery stage are limited. To compare the difference of epidemiological and clinical characteristics of COVID-19 involving 25 patients under 18 years old in recovery stage between confirmed and asymptomatic infections. Methods Retrospective, single-center cohort study of COVID-19 involving 25 patients under 18 years old in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of confirmed COVID-19 infections and asymptomatic infections were compared. Results Among the 25 COVID infections under 18 years old, 16 (64%) were mild or moderate confirmed cases, and 9 (36%) were asymptomatic. The shortest treatment period was 6 days, the longest 26 days, and the average treatment period 14 days. Four cases (44.4%) had visited Wuhan or had a living story in the city. There were 9 (100%) asymptomatic cases were familial cluster outbreak, with an average infection number was 6 cases among all families. The number of asymptomatic COVID-19 infections with leukopenia were significantly more than confirmed cases (p=0.04). Conclusions Leukopenia mostly occurred in asymptomatic COVID-19 infections under 18 years old compared with the confirmed patients.

positive: Coronavirus Disease 2019 (COVID-19) From the Point of View of Neurologists: Observation of Neurological Findings and Symptoms During the Combat Against a Pandemic. Some respiratory viruses have long been known to cause neurological involvement. A novel coronavirus, leading to severe acute respiratory syndrome, also called coronavirus disease 19 (COVID-19), seems to be a new member of neuroinvasive viruses. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps on spreading around the world rapidly, reports about the neurological manifestations associated with SARS-CoV-2, increases day by day. It is reported that a variety of symptoms and syndromes such as headache, dizziness, confusion, ataxia, epilepsy, ischemic stroke, neuropathic pain and myopathy are common especially in more severe COVID-19 patients. It is also suggested that the development of neurological complications is strongly associated with a poor outcome. On the other hand, hyposmia can be the unique symptom in COVID-19 carriers and this can serve as a marker for identifying the otherwise asymptomatically infected patients. It is thought that SARS-CoV-2 may cause neurological symptoms through direct or indirect mechanisms. Nevertheless, neuroinvasion capability of SARS-CoV2 is confirmed by the presence of the virus, in the cerebrospinal fluid of a COVID-19 patient with encephalitis, and this is proven by gene sequencing. In conclusion, during the COVID-19 pandemic, it is crucial to be aware of the possible neurological complications of the disease. Therefore, in this review, we aimed to report neurological manifestations associated with SARS-CoV-2 and possible underlying pathophysiological mechanisms. Due to the high homology of SARS-CoV-2 with other human coronaviruses such as SARS-CoV or Middle East Respiratory Syndrome (MERS)-CoV, reviewing the neurological involvement also associated with these coronaviruses will provide an idea about the long-term complications of COVID-19.

positive: Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life PURPOSE: COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. This topic is currently arousing great interest, and a growing number of papers are being published. Aim of this study is to investigate the timing of recovery from OD and GD in a real-life population hospitalized for COVID-19. METHODS: We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian non-intensive care wards. RESULTS: All 100 patients were Caucasian, mean age was 65 years, 60% were males. Forty-two patients (mean age 63 years) experienced subjective chemosensory dysfunctions (29 OD and 41 GD): the male/female ratio was 2:1; 83% reported a complete or near complete recovery at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, P = 0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, P = 0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, P = 0.0018). CONCLUSIONS: Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a population of hospitalized patients significantly older than those previously described, and the additional data on gender differences.

positive: Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic? Abstract Introduction SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. Development We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. Conclusions SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

positive: Evolution of Computed Tomography Manifestations in Five Patients Who Recovered from Coronavirus Disease 2019 (COVID-19) Pneumonia

positive: Long-term Positivity to SARS-CoV-2: A Clinical Case of COVID-19 with Persistent Evidence of Infection In December 2019, an outbreak of a new coronavirus (SARS-CoV-2) was reported in Hubei province in China. The disease has since spread worldwide and the World Health Organization declared it a pandemic on 11 March 2020. We describe the case of a 65-year-old woman who clinically recovered from COVID-19 but showed persistent infection with SARS-CoV-2 for 51 days. LEARNING POINTS: A case of persistent infection with SARS-CoV-2 is described. Some tests may pick up viral RNA fragments, giving a false positive result. The quarantining of infected patients to limit possible SARS-CoV-2 spread is important.

positive: [Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients]. Objective To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Methods Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. Results There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43±16) years vs. (52±16) years; t=2.10, P=0.040], longer hospital stay [(15±6)d vs. (19±7)d; t=2.70, P=0.009], higher dyspnea ratio (5.41% vs. 53.85%; χ2=18.90, P<0.001), lower nasal oxygen therapy ratio (81.08% vs. 19.23%;χ2=23.66, P<0.001), and higher bi-level positive airway pressure ventilation ratio (0 vs. 57.69%; χ2=25.62, P<0.001). Time from onset was (23±6) days in severe/critical group, significantly longer than that in mild/moderate group [(18±7) days] (t=3.40, P<0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% vs.10.81%;χ2=4.24, P=0.039) and lower ground-glass opacities ratio (15.38% vs. 67.57%; χ2=16.74, P<0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% vs.34.61%; χ2=13.43, P<0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% vs.10.81%; χ2=20.47, P<0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points vs. 7 (4,9) points; Z=3.81, P<0.001]. Conclusions The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.

positive: Liver injury in COVID-19: management and challenges

positive: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.

positive: Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge PURPOSE: To analyze clinical and thin-section computed tomographic (CT) data from the patients with coronavirus disease (COVID-19) to predict the development of pulmonary fibrosis after hospital discharge. MATERIALS AND METHODS: Fifty-nine patients (31 males, 28 females; mean age: 41 years, range: 25 to 70 years) with confirmed COVID-19 infection performed follow-up thin-section CT of the thorax. After 31.5 days of hospital admission, the results of thin-section CT were analyzed for parenchymal abnormality (ground-glass opacification, interstitial thickening, and consolidation) and evidence of fibrosis (parenchymal band, traction bronchiectasis, and irregular interfaces). Patients were analyzed based on the evidence of fibrosis and divided into two groups, group A (with CT evidence of fibrosis) and group B (without CT evidence of fibrosis). Patient demographics, length of stay (LOS), rate of intensive care unit (ICU) admission, peak C-reactive protein level, and CT score were compared between the two groups. RESULTS: Among the 59 patients, 89.8% (53/59) patients had a typical transition from early phase to advanced phase and advanced phase to dissipating phase. Out of 59 patients, 39% (23/59) patients developed fibrosis (group A), whereas 61% (36/59) patients did not show definite fibrosis (group B). Patients in group A were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), higher rate of ICU admission (21.7% (5/23) vs. 5.6% (2/36)), higher peak C-reactive protein level (30.7 vs. 18.1 mg/L), and higher maximal CT score (5.2 vs. 4.0) than those in group B. CONCLUSIONS: Pulmonary fibrosis may develop early in patients with COVID-19 after hospital discharge. Older patients with severe illness during treatment were more prone to develop fibrosis according to thin-section CT results.

positive: Effects of age and sex on recovery from COVID-19: Analysis of 5,769 Israeli patients

positive: Solid Organ Transplantation During the COVID-19 Pandemic Since December 2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly affected solid organ transplantation (SOT) worldwide and has become a threat to the lives of SOT recipients. Here, we have reviewed, condensed, and organized the available information on COVID-19 to provide recommendations to transplant healthcare workers. Our review of reported cases shows that the symptoms of SOT patients with COVID-19 are similar to those of the normal population, but their severity and outcomes are worse. Thus far, there is no evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly causes permanent damage to kidney, liver, or heart allografts.

positive: How do we recover from COVID-19? Helping diabetes teams foresee and prepare for the psychological harms The scale of the COVID-19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large-scale disasters indicates that following a first wave of admissions and deaths from COVID-19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long-term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second- and third-wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.

positive: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.

positive: Posttraumatic stress symptoms of health care workers during the corona virus disease 2019 Corona virus disease 2019 (COVID-19) outbreak has attracted worldwide attention. The COVID-19 outbreak is unique in its rapid transmission and results in heavy stress for the front-line health care workers (HCWs). The current study aimed to exam posttraumatic stress symptoms (PTSSs) of HCWs fighting for the COVID-19 and to evaluate their sleep quality after 1-month stressful suffering. Three hundred seventy-seven HCWs working in different provinces of China participated in the survey between February 1 and 5. The demographic information was collected first. Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) and the Pittsburgh Sleep Quality Index (PSQI) were selected to measure PTSSs and sleep quality. Results showed that 1 month after the outbreak, the prevalence of PTSSs was 3.8% in HCWs. Female HCWs were more vulnerable to PTSSs with hazard ratio of 2.136 (95% CI = 1.388-3.286). HCWs with higher exposure level also significantly rated more hyperarousal symptoms (hazard ratio = 4.026, 95% CI = 1.233-13.140). There was a significant difference of sleep quality between participants with and without PTSSs (z value = 6.014, p < .001) and among different groups with various contact frequencies (chi-square = 7.307, p = .026). Path analysis showed that there was a significant indirect effect from exposure level to PTSSs through sleep quality (coefficient = 1.750, 95% CI of Boostroop test = 0.543-2.998). In summary, targeted interventions on sleep contribute to the mental recovery during the outbreak of COVID-19. Understanding the mental health response after a public health emergency might help HCWs and communities prepare for a population's response to disaster.

positive: Addressing male sexual and reproductive health in the wake of COVID-19 outbreak PURPOSE: The COVID-19 pandemic, caused by the SARS-CoV-2, represents an unprecedented challenge for healthcare. COVID-19 features a state of hyperinflammation resulting in a “cytokine storm”, which leads to severe complications, such as the development of micro-thrombosis and disseminated intravascular coagulation (DIC). Despite isolation measures, the number of affected patients is growing daily: as of June 12th, over 7.5 million cases have been confirmed worldwide, with more than 420,000 global deaths. Over 3.5 million patients have recovered from COVID-19; although this number is increasing by the day, great attention should be directed towards the possible long-term outcomes of the disease. Despite being a trivial matter for patients in intensive care units (ICUs), erectile dysfunction (ED) is a likely consequence of COVID-19 for survivors, and considering the high transmissibility of the infection and the higher contagion rates among elderly men, a worrying phenomenon for a large part of affected patients. METHODS: A literature research on the possible mechanisms involved in the development of ED in COVID-19 survivors was performed. RESULTS: Endothelial dysfunction, subclinical hypogonadism, psychological distress and impaired pulmonary hemodynamics all contribute to the potential onset of ED. Additionally, COVID-19 might exacerbate cardiovascular conditions; therefore, further increasing the risk of ED. Testicular function in COVID-19 patients requires careful investigation for the unclear association with testosterone deficiency and the possible consequences for reproductive health. Treatment with phosphodiesterase-5 (PDE5) inhibitors might be beneficial for both COVID-19 and ED. CONCLUSION: COVID-19 survivors might develop sexual and reproductive health issues. Andrological assessment and tailored treatments should be considered in the follow-up.

positive: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area Importance: There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective: To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants: Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures: Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures: Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results: A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

positive: Neurological complications of COVID-19: a preliminary review

positive: COVID 19 associated encephalopathy: Neurological manifestation of COVID-19 Covid-19 is a viral disease, also known as SARS-Cov-2, was first reported in Wuhan China, December 2019. Respiratory manifestations from the induced acute lung injury were the most common reported findings. Few cases showed extrapulmonary manifestations. Covid-19 associated neurological manifestations have not been widely reported. In this report, we describe a case of encephalopathy in a patient with Covid-19 infection. Abbreviations: SARS-Cov-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019;; RT-PCR, Reverse transcription polymerase chain reaction; ED, emergency department; ICU, intensive care unit; GCS, Glasgow Coma Scale; HRCT, high resolution computed tomography; CT, computed tomography; MRI, magnetic resonance imaging; FLAIR, fluid attenuated inversion recovery; ADC, apparent diffusion coefficient; DWI: diffusion weighted imaging; CNS, central nervous system.

positive: Concern coronavirus may trigger post-viral fatigue syndromes

positive: Hepatic complications of COVID‐19 and its treatment COVID‐19 is highly contagious and has a variety of clinical manifestations, it can affect a number of other organs in addition to the lungs, and liver injury may occur. SARS‐CoV‐2 can cause liver injury through systemic inflammatory response syndrome (SIRS), cytokine storms, ischemia‐reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via ACE2. Clinical studies have found that liver injury in COVID‐19 patients mainly manifests as abnormal liver biochemical indicators, but there have been no reports of liver failure caused by this disease. The number of COVID‐19 patients with liver injury is increasing, and the incidence of liver injury in COVID‐19 patients with severe disease are higher than in patients with mild disease. Liver injury may be a risk factor for progresses and worsens in patients with COVID‐19, and it is necessary to pay attention to the occurrence of liver injury in the diagnosis and treatment of COVID‐19. This article is protected by copyright. All rights reserved.

positive: A Case of COVID-19 Infection With Delayed Thromboembolic Complication on Warfarin Novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented threat to humanity with more than eight million infections and 450,000 deaths reported worldwide so far. The spectrum of the disease varies from mild asymptomatic infection to severe disease with rapid progression to acute respiratory distress syndrome and multiorgan failure. It is associated with a prothrombotic state and hence there is a risk of thromboembolic complications in critically ill patients, even after recovery. However, the duration of prothrombotic risk after recovery is yet to be determined. We present the case of a 78-year-old man with a history of atrial fibrillation on warfarin who had been recently discharged to a nursing home after recovering from COVID-19 pneumonia and presented to the emergency department a month later with worsening shortness of breath and cough. He was found to have worsening respiratory failure with multiple segmental pulmonary emboli, despite being on warfarin, and supratherapeutic international normalized ratio (INR). He required mechanical ventilation and was started on steroids and therapeutic enoxaparin anticoagulation. This case highlights the risk of delayed thromboembolic complications in patients with COVID-19 infection and the need to identify the subgroup of patients with a higher risk of thromboembolism, such as discharges to nursing homes and those in need of oxygen requirement; and those with underlying comorbid conditions that may require anticoagulation for a longer duration. The role of heparin is being increasingly investigated in patients with COVID-19 infection; however, the role of other anticoagulants such as warfarin is yet to be defined.

positive: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19() INTRODUCTION: Sudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate. OBJECTIVE: To characterize patients with sudden olfactory disfunction during the COVID-19 pandemic, especially their recovery data. METHODS: An online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1(st), 2020. RESULTS: 253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p = 0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p = 0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p = 0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p = 0.04). CONCLUSION: Positive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.

positive: Does SARS-CoV-2 infection cause chronic neurological complications? The current pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has created an unparalleled health crisis. Besides the acute respiratory infection, CoVs are neuroinvasive causing additional inflammation and neurodegeneration. This is likely also true of SARS-CoV-2 given reports of neurological manifestations in coronavirus disease 2019 (COVID-19) positive patients. Older adults > 65 years of age constitute a high-risk group prone to severe infection and death. Despite the higher mortality rate, a majority of cases are expected to recover and survive from this viral outbreak. But, the long-term consequences of SARS-CoV-2 neuroinfection are unknown. We discuss these potential chronic changes to the central nervous system (CNS) in relation to accelerated brain aging and age-related neurodegenerative disorders.

positive: Detection of lung hypoperfusion in Covid-19 patients during recovery by digital imaging quantification Purpose. A large number of patients affected by the SARS-Cov-2 virus worldwide undergo recovery of symptoms in about one month. Among these patients, the healing process is still under observation, with some patients in need of careful clinical monitoring. While the radiological findings have been shown to regress almost completely, little knowledge is available at the moment about other complications in the lung and in other organs. We then investigated the lung perfusion conditions in patients affected by COVID- 19 during recovery. Method. We retrospectively studied 20 patients, from 14 to 60 days after resolution of the COVID-19 symptoms, using chest CT. In a subgroup of 5 patients contrasted CT was used. Beside normal radiological evaluation of lung tissue, perfusion conditions were evaluated by digital image processing in the lung volume automatically segmented. Results. Pulmonary lung evaluation showed that COVID-19 pneumonia almost completely regressed, with mild focal areas affected by fibrous stripes. In patients that reported dyspnea, lung CT showed complete resolution of interstitial changes. Quantification of lung perfusion condition by contrasted CT, showed that dyspnea in 3 patients was associated with areas of hypoperfusion, while in 2 patients not reporting dyspnea perfusion conditions were comparable to normal controls. Conclusions. Although we obtained preliminary data, this is the first report on quantitative evaluation of hypoperfused lung tissue detected in recovering COVID-19 patients. These results suggest the need to further investigate these patients and to redefine the role of CT evaluation for diagnostic purposes as well as for evaluation of potential treatments.

positive: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

positive: Disappearance of antibodies to SARS-CoV-2 in a Covid-19 patient after recovery A newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19) across the world. An understanding of the antibody responses to the viral components is very important for diagnosis and vaccine development. We herein estimated the longevity of specific antibodies against SARS-CoV-2, and reported antibodies disappeared in a moderate COVID-19 patient within 3 months after the onset of the symptoms.

positive: Clinical characteristics of imported and second-generation COVID-19 cases outside Wuhan, China: A multicenter retrospective study Background The mortality of COVID-19 differs between countries and regions. By now, reports on COVID-19 are largely focused on first-generation cases. This study aimed to clarify the clinical characteristics of imported and second-generation cases. Methods This retrospective, multicenter cohort study included 134 confirmed COVID-19 cases from 9 cities outside Wuhan. Epidemiological, clinical and outcome data were extracted from medical records and were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. Results 34.3% of the 134 patients were severe cases, and 11.2% had complications. As of March 7, 2020, 91.8% patients were discharged and one patient (0.7%) died. The median age was 46 years. The median interval from symptom onset to hospital admission was 4.5 (IQR 3-7) days. The median lymphocyte count was 1.1*109/L. Age, lymphocyte count, CRP, ESR, DBIL, LDH, HBDH showed difference between severe and no-severe cases (all P<0.05). Baseline lymphocyte count was higher in the survived patients than in the non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The IL-6 level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest CT images in 51.5% of the pneumonia cases. Conclusion Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.

positive: Myocardial injury and COVID-19: Possible mechanisms Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.

positive: Epidemiology of CoViD-19 Pandemic: Recovery and mortality ratio around the globe Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.

positive: Prior and Novel Coronaviruses, COVID-19, and Human Reproduction: What Is Known? Structured Abstract Objective To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. Design Review of English publications in PubMed and Embase to April 6, 2020. Methods Manuscripts were screened for reports including coronavirus, reproduction, including pathophysiology and pregnancy. Intervention(s) None. Main Outcome Measure(s) Reproductive outcomes; effects on gametes; pregnancy outcomes; neonatal complications. Results Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. SARS-CoV-1 may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following COVID-19 infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-CoV-2 adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or MERS, but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. COVID-19 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. Conclusion COVID-19 infection may adversely affect some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

positive: Establishment of a COVID‐19 Recovery Unit in a Veteran Affairs (VA) Post‐Acute Facility Coronavirus disease 19 (COVID‐19) is now an epidemic of global proportion with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long‐term care facilities. This health catastrophe has challenged healthcare facilities’ capacity to deliver care to not only COVID‐19 patients but all patients who need hospital care. We report on a novel approach of utilizing long‐term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID‐19 patients.

positive: Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

positive: Coronavirus disease (COVID-19) in neurology and neurosurgery: A scoping review of the early literature Coronavirus disease 2019 (COVID-19) is a devastating respiratory illness that has dramatically changed the medical landscape around the world. In parallel with a rise in the number of cases globally, the COVID-19 literature has rapidly expanded with experts around the world disseminating knowledge and collaborating on best practices. To date, the literature has predominantly consisted of case reports, case series, and systemic protocols for dealing with this deadly disease from a plethora of specialties with larger observational and randomized studies only now starting to emerge. This scoping review of MEDLINE, EMBASE, SCOPUS, and the Cochrane Library aims to evaluate and summarize the current status of the COVID-19 literature at it applies to neurology and neurosurgery. Neurological symptomatology, neurological risk factors for poor prognosis, pathophysiology for neuroinvasion, and actions taken by neurological or neurosurgical services to manage the current COVID-19 crisis are reviewed.

positive: Follow-up studies in COVID-19 recovered patients - is it mandatory? The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.

positive: Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation- and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers.

positive: Abnormal pulmonary function in COVID-19 patients at time of hospital discharge In discharged survivors with COVID-19, impairment of diffusion capacity is the most common abnormality of lung function followed by restrictive ventilatory defect, which are both associated with the severity of the disease. Pulmonary function test (not onl

positive: COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System. Coronavirus disease 19 (COVID-19) is an infectious disease caused by SARS-Cov-2, resulting in severe acute respiratory syndrome, with high potential of spreading and infecting humans worldwide. Since January 2020, when the virus was identified in humans, the literature on COVID-19 has grown exponentially, and extra respiratory symptoms including neurological symptoms are increasingly highlighted. These neurological disorders are grouped into several categories, ranging from non-specific and moderate symptoms such as headache, myalgia and hyposmia to severe symptoms including cerebrovascular disease and intracranial infections. Severe neurological symptoms such as acute cerebrovascular disease occur only in a minority of patients with usual risk factor, and are associated with poor outcome. However, most COVID-19 patients exhibit only minor or mild neurological symptoms. Given the high and increasing number of publications reporting neurological involvements of SARS-Cov-2, we think providing an update for neurological complications of COVID-19 could be useful for physician and especially young trainees in neurology and neurosurgery. Indeed, in this review we discuss several neurological aspects reported in the literature to date, including the evidence and pathways of the neuro-invasion in COVID-19, and the main neurological disorders reported in the literature to date, as well as the future perspectives and the potential long term consequence of current neuro-infection in COVID-19 patients.

positive: Clinical outcomes and immunologic characteristics of Covid-19 in people with HIV We performed a retrospective study of Covid-19 in people with HIV (PWH). PWH with Covid-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin-6, interleukin-8, and TNF-alpha were commonly elevated. In all, 19/72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of Covid-19 despite ART and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.

positive: Coronaviruses and the cardiovascular system: acute and long-term implications

positive: Comorbidity and its Impact on Patients with COVID-19 A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, in December 2019. Since then, the virus has made its way across the globe to affect over 180 countries. SARS-CoV-2 has infected humans in all age groups, of all ethnicities, both males and females while spreading through communities at an alarming rate. Given the nature of this virus, there is much still to be learned; however, we know that the clinical manifestations range from a common cold to more severe diseases such as bronchitis, pneumonia, severe acute respiratory distress syndrome (ARDS), multi-organ failure, and even death. It is believed that COVID-19, in those with underlying health conditions or comorbidities, has an increasingly rapid and severe progression, often leading to death. This paper examined the comorbid conditions, the progression of the disease, and mortality rates in patients of all ages, infected with the ongoing COVID-19 disease. An electronic literature review search was performed, and applicable data was then collected from peer-reviewed articles published from January to April 20, 2020. From what is known at the moment, patients with COVID-19 disease who have comorbidities, such as hypertension or diabetes mellitus, are more likely to develop a more severe course and progression of the disease. Furthermore, older patients, especially those 65 years old and above who have comorbidities and are infected, have an increased admission rate into the intensive care unit (ICU) and mortality from the COVID-19 disease. Patients with comorbidities should take all necessary precautions to avoid getting infected with SARS CoV-2, as they usually have the worst prognosis.

positive: Chronic pain following COVID-19: implications for rehabilitation

positive: Does COVID-19 cause permanent damage to olfactory and gustatory function? The objective of this study was to investigate the status of COVID-19 patients with sudden anosmia and dysgeusia using an olfactory dysfunction questionnaire highlighting recovery times. This prospective study included 75 patients who completed a patient-reported outcome questionnaire. Among these, 46 patients completed an olfactory evaluation based on the duration of anosmia and dysgeusia. The olfactory evaluation revealed that 24% (N=18) of patients had mild hyposmia, 13% (N=10) had moderate hyposmia, 30% (N=23) had severe hyposmia, 32% (N=24) had anosmia, and 100% had dysgeusia (N=75). The viral load significantly decreased throughout the 17 days following the onset of the olfactory disorder. The purpose of this study was to understand whether patients with COVID-19 can recover olfactory and gustatory function, in contrast to patients with other rhinoviruses and inflammatory diseases such as rhinosinusitis chronic and rhinosinusitis with polyps. These preliminary clinical findings indicate that the relatively rapid recovery of olfactory and gustative function can mean a resolution of viral infection in most patients. The present study suggests that coronavirus can induce olfactory dysfunction but not permanent damage. Olfactory and gustatory functional impairment has been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome. Our study supports the need to add anosmia and dysgeusia to the list of symptoms used in screening tools for possible COVID-19 infection.

positive: Considering the potential for an increase in chronic pain after the COVID-19 pandemic

positive: Nervous system involvement after infection with COVID-19 and other coronaviruses Abstract Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

positive: Cardiovascular disease and COVID-19 Abstract Background and aims Many patients with coronavirus disease 2019 (COVID-19) have underlying cardiovascular (CV) disease or develop acute cardiac injury during the course of the illness. Adequate understanding of the interplay between COVID-19 and CV disease is required for optimum management of these patients. Methods A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. Results Respiratory illness is the dominant clinical manifestation of COVID-19; CV involvement occurs much less commonly. Acute cardiac injury, defined as significant elevation of cardiac troponins, is the most commonly reported cardiac abnormality in COVID-19. It occurs in approximately 8–12% of all patients. Direct myocardial injury due to viral involvement of cardiomyocytes and the effect of systemic inflammation appear to be the most common mechanisms responsible for cardiac injury. The information about other CV manifestations in COVID-19 is very limited at present. Nonetheless, it has been consistently shown that the presence of pre-existing CV disease and/or development of acute cardiac injury are associated with significantly worse outcome in these patients. Conclusions Most of the current reports on COVID-19 have only briefly described CV manifestations in these patients. Given the enormous burden posed by this illness and the significant adverse prognostic impact of cardiac involvement, further research is required to understand the incidence, mechanisms, clinical presentation and outcomes of various CV manifestations in COVID-19 patients.

positive: Risk Factors Associated With Long-Term Hospitalization in Patients With COVID-19: A Single-Centered, Retrospective Study Background: The coronavirus disease 19 (COVID-19) pandemic has become a global threat. Few studies have explored the risk factors for the recovery time of patients with COVID-19. This study aimed to explore risk factors associated with long-term hospitalization in patients with COVID-19. Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 hospitalized in a hospital in Wuhan by March 30, 2020, were included. Demographic, clinical, laboratory, and radiological data from COVID-19 patients on hospital admission were extracted and were compared between the two groups, defined as short- and long-term hospitalization, respectively according to the median hospitalization time. Univariable and multivariable logistic regression methods were performed to identify risk factors associated with long-term hospitalization in patients with COVID-19. Results: A total of 125 discharged patients with COVID-19 were reviewed, including 123 general patients and two severe patients. The median hospitalization time was 13.0 days (IQR 10.0–17.0). Among them, 66 patients were discharged <14 days (short-term group) and 59 patients were discharged ≥14 days (long-term group). Compared with the short-term group, patients in the long-term group had significantly higher levels of C-reactive protein (P = 0.000), troponin I (P = 0.002), myoglobin (P = 0.037), aspartate aminotransferase (P = 0.005), lactic dehydrogenase (P = 0.000), prothrombin time (P = 0.030), fibrinogen (P = 0.000), and D-dimer (P = 0.006), but had significantly lower levels of lymphocyte count (P = 0.001), platelet count (P = 0.017), albumin (P = 0.001), and calcium (P = 0.000). Additionally, the incidences of hypocalcemia (P = 0.001), hyponatremia (P = 0.021), hypochloremia (P = 0.019), and bilateral pneumonia (P = 0.000) in the long-term group were significantly higher than those in the short-term group. Multivariable regression showed that hypocalcemia (P = 0.007, OR 3.313, 95% CI 1.392–7.886), hypochloremia (P = 0.029, OR 2.663, 95% CI 1.104–6.621), and bilateral pneumonia (P = 0.009, OR 5.907, 95% CI 1.073–32.521) were independent risk factors associated with long-term hospitalization in patients with COVID-19. Furthermore, a ROC curve where the area under the ROC was 0.766 for retained variables is presented. Conclusions: Hypocalcemia, hypochloremia, and bilateral pneumonia on hospital admission were independent risk factors associated with long-term hospitalization in patients with COVID-19. To the best of our knowledge, this is the first study to highlight the importance of electrolyte imbalance in predicting the hospitalization time of patients with COVID-19.

positive: Identification of IgG antibody response to SARS-CoV-2 spike protein and its receptor binding domain does not predict rapid recovery from COVID-19 Diagnostic testing and evaluation of patient immunity against the novel severe acute respiratory syndrome (SARS) corona virus that emerged last year (SARS-CoV-2) are essential for health and economic crisis recovery of the world. It is suggested that potential acquired immunity against SARS-CoV-2 from prior exposure may be determined by detecting the presence of circulating IgG antibodies against viral antigens, such as the spike glycoprotein and its receptor binding domain (RBD). Testing our asymptomatic population for evidence of COVID-19 immunity would also offer valuable epidemiologic data to aid health care policies and health care management. Currently, there are over 100 antibody tests that are being used around the world without approval from the FDA or similar regulatory bodies, and they are mostly for rapid and qualitative assessment, with different degrees of error rates. ELISA-based testing for sensitive and rigorous quantitative assessment of SARS-CoV-2 antibodies can potentially offer mechanistic insights into the COVID-19 disease and aid communities uniquely challenged by limited financial resources and access to commercial testing products. Employing recombinant SARS-CoV-2 RBD and spike protein generated in the laboratory, we devised a quantitative ELISA for the detection of circulating serum antibodies. Serum from twenty SARS-CoV-2 RT-PCR confirmed COVID-19 hospitalized patients were used to detect circulating IgG titers against SARS-CoV-2 spike protein and RBD. Quantitative detection of IgG antibodies to the spike glycoprotein or the RBD in patient samples was not always associated with faster recovery, compared to patients with borderline antibody response to the RBD. One patient who did not develop antibodies to the RBD completely recovered from COVID-19. In surveying 99 healthy donor samples (procured between 2017-February 2020), we detected RBD antibodies in one donor from February 2020 collection with three others exhibiting antibodies to the spike protein but not the RBD. Collectively, our study suggests that more rigorous and quantitative analysis, employing large scale sample sets, is required to determine whether antibodies to SARS-CoV-2 spike protein or RBD is associated with protection from COVID-19 disease. It is also conceivable that humoral response to SARS-CoV-2 spike protein or RBD works in association with adaptive T cell response to determine clinical sequela and severity of COVID-19 disease.

positive: A special symptom of olfactory dysfunction in coronavirus disease 2019: report of three cases Three patients of coronavirus disease (COVID-19) showed the symptoms of olfactory dysfunction. Clinical characteristics and treatment were retrospective analyzed. Olfactory disorders are uncommon symptoms of COVID-19 in China. Early diagnosis and intervention are keys to the recovery of olfactory disorders. Particular attention should be devoted to olfactory dysfunction.

positive: Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19 This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.

positive: The effect of massage on the quality of life in patients recovering from COVID-19: A systematic review protocol BACKGROUND: There is a worldwide outbreak of covid-19, and as the number of patients increases, more and more patients are recovering. Massage is used as an alternative therapy. Currently, there are no relevant articles for systematic review. METHODS: We will search the randomized controlled trials related to acupuncture therapy and postoperative anorectal diseases from inception to January 2020. The following database is our focus area: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-Fang Database. All published randomized controlled trials in English or Chinese related to massage for COVID-19 will be included. Primary outcome asthe influence of massage on the quality of life of convalescent patients. Secondary outcomes were accompanying symptoms (such as myalgia, expectoration, stuffiness, runny nose, pharyngalgia, anhelation, chest distress, dyspnea, crackles, headache, nausea, vomiting, anorexia, diarrhea) disappear rate, negative COVID-19 results rate on 2 consecutive occasions (not on the same day), average hospitalization time, clinical curative effect, and improved quality of life. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether massage is an effective intervention on the quality of life in patients recovering. PROSPERO REGISTRATION NUMBER: CRD42020181398.

positive: Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong. This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.

positive: Giving voice to those directly affected by the COVID-19 pandemic – the experience and reflections of a person with dementia The coronavirus disease 2019 (COVID-19) pandemic presents unprecedented challenges to society. Behind the daily tally of deaths and cases of infection are individuals and families who are experiencing the ultimate consequence of this disease. Every aspect of our lives has been affected and these affects are amplified for those who have to cocoon and have conditions such as dementia. There is little opportunity to directly hear the experience of those ‘vulnerable adults’ who have been self-isolating for many weeks now. This letter takes the form of a reflective conversation with a person living with dementia. Honouring the principles of public and patient involvement (PPI), it is an attempt to give voice to the experience of one of the many thousands of vulnerable people during the COVID-19 pandemic. As well as describing the effect on her daily life, Helen describes what supports would help at this time. While the focus of attention at the moment is rightly on dealing with the effects of the virus in nursing homes, the many thousands of people living with dementia in the community should not be forgotten.

positive: Are COVID-19 survivors at increased risk for suicide?

negative: Consecuencias maternas y neonatales de la infección por coronavirus COVID-19 durante el embarazo: una scoping review./ [Maternal and neonatal consequences of coronavirus COVID-19 infection during pregnancy: a scoping review] BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization, which can have negative consequences for pregnant women and their newborns. The aim of this study was to explore the available knowledge on the consequences of developing COVI-19 in pregnant women and their neonates. METHODS: Scoping Review, in which the search for articles was conducted using DeCS ("pregnancy", "coronavirus", "health") and MeSH ("pregnan*", "pregnant women", "coronavirus"), linking the terms with the Boolean AND operator. Databases used were Web of Science, Scopus, BVS, Scielo and CUIDEN. In addition, the PRISMA methodology was applied. RESULTS: Ten studies were identified that assessed maternal and neonatal health after maternal COVID-19 infection. Pregnant women seem to had no serious symptoms. Neonates appeared to be affected to a greater extent. A death was reported in a premature newborn whose mother had COVID-19 pneumonia. There did not appear to be vertical transmission from mother to child. Nevertheless, this information was not conclusive. CONCLUSIONS: COVID-19 appears to be more benign with pregnant women than with their neonates.

negative: Increased Detection coupled with Social Distancing and Health Capacity Planning Reduce the Burden of COVID-19 Cases and Fatalities: A Proof of Concept Study using a Stochastic Computational Simulation Model Objective: In absence of any vaccine, the Corona Virus Disease 2019 (COVID-19) pandemic is being contained through a non-pharmaceutical measure termed Social Distancing (SD). However, whether SD alone is enough to flatten the epidemic curve is debatable. Using a Stochastic Computational Simulation Model, we investigated the impact of increasing SD, hospital beds and COVID-19 detection rates in preventing COVID-19 cases and fatalities. Research Design and Methods: The Stochastic Simulation Model was built using the EpiModel package in R. As a proof of concept study, we ran the simulation on Kasaragod, the most affected district in Kerala. We added 3 compartments to the SEIR model to obtain a SEIQHRF (Susceptible-Exposed-Infectious-Quarantined-Hospitalised-Recovered-Fatal) model. Results: Implementing SD only delayed the appearance of peak prevalence of COVID-19 cases. Doubling of hospital beds could not reduce the fatal cases probably due to its overwhelming number compared to the hospital beds. Increasing detection rates could significantly flatten the curve and reduce the peak prevalence of cases (increasing detection rate by 5 times could reduce case number to half). Conclusions: An effective strategy to contain the epidemic spread of COVID-19 in India is to increase detection rates in combination with SD measures and increase in hospital beds.

negative: COVID-19 related mortality and spread of disease in long-term care: first findings from a living systematic review of emerging evidence Background: Policy responses to mitigate the impact of the COVID-19 pandemic on long-term care (LTC) require robust and timely evidence on mortality and spread of the disease in these settings. The aim of this living systematic review is to synthesise early international evidence on mortality rates and incidence of COVID-19 among people who use and provide LTC. Methods: We report the initial findings of a living systematic review (CRD42020183557), including studies identified through database searches up to 29 May 2020. We searched seven databases (MEDLINE; Embase; CINAHL Plus; Web of Science; Global Health; WHO COVID-19 Research Database; medRxiv) to identify all studies reporting primary data on COVID-19 related mortality and incidence of disease among LTC users and staff. We excluded studies not focusing on LTC. Included primary studies were critically appraised and results on number of deaths and COVID-19 related mortality rates, case fatality rates, and excess deaths (co-primary outcomes), as well as incidence of disease, hospitalisations, and ICU admissions were synthesised narratively. We further included official figures on number of deaths in LTC. Findings: A total of 30 study reports for 27 unique primary studies or outbreak reports were included. Outbreak investigations in LTC facilities found COVID-19 incidence rates of between 0.0% and 71.7% among residents and between 1.5% and 64.0% among staff. Mortality rates varied from 0.0% to 9.9% of all residents at outbreak facilities, with case fatality rates between 0.0% and 33.7%. In included studies, no LTC staff members had died. LTC residents accounted for between 0% (Hong Kong) and 82% (Canada) of COVID-related deaths, according to official figures. Interpretation: Long-term care users have been particularly vulnerable to the COVID-19 pandemic. However, we found wide variation in spread of disease and mortality rates between outbreaks at individual LTC facilities. Further research into the factors determining successful prevention and containment of COVID-19 outbreaks is needed to protect long-term care users and staff.

negative: Age-adjusted associations between comorbidity and outcomes of COVID-19: a review of the evidence Background: Current evidence suggests that older people and people with underlying comorbidities are at increased risk of severe disease and death following hospitalisation with COVID-19. As comorbidity increases with age, it is necessary to understand the age-adjusted relationship between comorbidity and COVID-19 outcomes, in order to enhance planning capabilities and our understanding of COVID-19. Methods: We conducted a rapid, comprehensive review of the literature up to 10 April 2020, to assess the international empirical evidence on the association between comorbidities and severe or critical care outcomes of COVID-19, after accounting for age, among hospitalised patients with COVID-19. Results: After screening 579 studies, we identified seven studies eligible for inclusion and these were synthesised narratively. All were from China. The emerging evidence base mostly indicates that after adjustment for age (and in some cases other potential confounders), obesity, hypertension, diabetes mellitus, chronic obstructive airways disease (COPD), and cancer are all associated with worse outcomes. The largest study, using a large nationwide sample of COVID-19 patients in China, found that those with multiple comorbidities had more than twice the risk of a severe outcome or death compared with patients with no comorbidities, after adjusting for age and smoking (HR=2.59, 95% CI 1.61, 4.17). Conclusions: This review summarises for clinicians, policymakers, and academics the most robust evidence to date on this topic, to inform the management of patients and control measures for tackling the pandemic. Given the intersection of comorbidity with ethnicity and social disadvantage, these findings also have important implications for health inequalities. As the pandemic develops, further research should confirm these trends in other settings outside China and explore mechanisms by which various underlying health conditions increase risk of severe COVID-19.

negative: Estimating the risk of 2019 Novel Coronavirus death during the course of the outbreak in China, 2020 Since the first case of Novel Coronavirus (2019-nCov) was identified in December 2019 in Wuhan City, China, the number of cases continues to grow across China and multiple cases have been exported to other countries. The cumulative number of reported deaths is at 637 as of February 7, 2020. Here we statistically estimated the time-delay adjusted death risk for Wuhan as well as for China excluding Wuhan to interpret the current severity of the epidemic in China. We found that the latest estimates of the death risk in Wuhan could be as high as 20% in the epicenter of the epidemic whereas we estimate it ~1% in the relatively mildly-affected areas. Because the elevated death risk estimates are likely associated with a breakdown of the medical/health system, enhanced public health interventions including social distancing and movement restrictions should be effectively implemented to bring the epidemic under control.

negative: Effect and enlightenment of rehabilitation medicine in COVID-19 management. Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.

negative: COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus An epidemic of extreme respiratory deterrence, pneumonia and shortness of breath, the SARS-CoV-2 viral infection began in Wuhan, Hubei Province, China in December 2019, and rapidly spread across China and beyond, with human to human transmission. On February 12, 2020, World Health Organization officially named the new coronavirus disease as coronavirus disease 19 (COVID-19). Most COVID-19 patients were diagnosed with pneumonia and many were treated using Chinese medicines and other secondary therapies. As of April 22, 2020, the total figure of infected patients has crossed 2.6 million people worldwide with over 180,000 deaths and 700,000 patients that have recovered. Preliminary reports suggest that certain drugs, such as chloroquine and antiviral nucleotide analogues such as remdesivir, which inhibit viral replication, can target the new coronavirus, although their usefulness in the clinic is still under debate. An expert US committee developed the US NIH guidelines for COVID-19 treatment, which was just released and will be regularly updated. This manuscript reviews the epidemiology, etiology, mortality, COVID-19 clinical symptoms, and potential therapeutic drugs, while highlighting the seriousness and damage-induced by SARS-CoV-2.

negative: Short-term and long-term outcomes of postinfarction ventricular septal perforation. PURPOSE Ventricular septal perforation represents a serious complication after acute myocardial infarction. This study aimed to evaluate the short-term and longterm outcomes of postinfarction ventricular septal perforation (VSP). METHODS We evaluated outcomes for VSP repair for 42 patients over 19 years. A retrospective analysis of clinical records, risk factors for hospital death, and long-term survival was performed. RESULTS In-hospital mortality was 33.3%. The most common cause of hospital death was left-sided heart failure. A low ejection fraction and short time interval from acute myocardial infarction to the onset of VSP were significant risk factors. The actuarial survival rates of in-hospital survivors at 5 and 10 years were 81.7% and 43.5%, respectively. There were 17 cardiac events among the survivors during the follow-up period. The most influential factor affecting long-term outcomes was the number of diseased coronary arteries. CONCLUSION The long-term survival outcome of VSP patients during the postoperative period was comparatively good, but the prognosis of VSP patients with multivessel disease was not satisfactory because of congestive heart failure or ventricular arrhythmia. We believe that postoperative medical treatment for preventing cardiac remodeling is important for improving long-term survival outcomes in such patients.

negative: Theoretical basis and effect characteristics of andrographolide against COVID-19/ 穿心莲内酯类制剂抗新型冠状病毒肺炎的相关理论依据和作用特点 Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly in China. National Health Commission of the People’s Republic of China and local departments have released a number of diagnosis and treatment plans for COVID-19. Some plans recommend Xiyanping Injection for the clinical treatment of COVID-19. The active component of the drug is the total sulfonate of andrographolide, which is a derivative of andrographolide. This paper summarized the pharmacological action and clinical application of andrographolide, and proposed that it has the functions of clearing heat and detoxification, anti-bacterial and anti-inflammatory, and definite therapeutic effect on respiratory system diseases including viral pneumonia and upper respiratory tract infection, and a large number of clinical data have been accumulated. Andrographolide has a potential antiviral effect on the treatment of COVID-19, and can reduce the level of inflammation in patients, improve respiratory symptoms, inhibit concurrent bacterial infection, and improve the body immunity. At the same time, it will not bring the immunosuppressive effect of hormone drugs, and the incidence of adverse reactions is low. In addition, Andrographolide has certain hepatoprotective effects and clinical value for treating cardiovascular diseases in clinical experience, suggesting that it may have some protective effects on drug-induced liver injury, heart injury and liver injury caused by durgs against COVID-19, but further clinical verification is needed. The pharmacological action and clinical application of andrographolide are summarized. This paper also analyzes the etiology, pathogenesis and dialectical treatment of COVID-19 from the perspective of traditional Chinese medicine, and points out that the treatment of COVID-19 with andrographolide is consistent with the theory of traditional Chinese medicine.

negative: COVIDiagnosis-Net: Deep Bayes-SqueezeNet based Diagnostic of the Coronavirus Disease 2019 (COVID-19) from X-Ray Images The COVID-19 outbreak has a tremendous impact on global health and the daily life of people still living in more than two hundred countries. The crucial action to gain the force in the fight of COVID-19 is to have powerful monitoring of the site forming infected patients. Most of the initial tests rely on detecting the genetic material of the coronavirus, and they have a poor detection rate with the time-consuming operation. In the ongoing process, radiological imaging is also preferred where chest X-rays are highlighted in the diagnosis. Early studies express the patients with an abnormality in chest X-rays pointing to the presence of the COVID-19. On this motivation, there are several studies cover the deep learning-based solutions to detect the COVID-19 using chest X-rays. A part of the existing studies use non-public datasets, others perform on complicated Artificial Intelligent (AI) structures. In our study, we demonstrate an AI-based structure to outperform the existing studies. The SqueezeNet that comes forward with its light network design is tuned for the COVID-19 diagnosis with Bayesian optimization additive. Fine-tuned hyperparameters and augmented dataset make the proposed network perform much better than existing network designs and to obtain a higher COVID-19 diagnosis accuracy.

negative: The COVID-19 Global Pandemic: Implications for People With Schizophrenia and Related Disorders The coronavirus disease-19 (COVID-19) global pandemic has already had an unprecedented impact on populations around the world, and is anticipated to have a disproportionate burden on people with schizophrenia and related disorders. We discuss the implications of the COVID-19 global pandemic with respect to: (1) increased risk of infection and poor outcomes among people with schizophrenia, (2) anticipated adverse mental health consequences for people with schizophrenia, (3) considerations for mental health service delivery in inpatient and outpatient settings, and (4) potential impact on clinical research in schizophrenia. Recommendations emphasize rapid implementation of measures to both decrease the risk of COVID-19 transmission and maintain continuity of clinical care and research to preserve safety of both people with schizophrenia and the public.

negative: Involvement of Cardiovascular System As The Critical Point in Coronavirus Disease 2019 (COVID-19) Prognosis and Recovery The novel coronavirus disease (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and especially existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of COVID-19 patients.

negative: Expression of Recombinant Antibodies Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

negative: Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2 Objective To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. Study Design This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). Results Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. Conclusion Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. Key Points: Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth. Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth. Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed.

negative: Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis Substance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registration CRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.

negative: Increase in COVID‐19 cases and case‐fatality and case‐recovery rates in Europe: A cross‐temporal meta‐analysis The new coronavirus (COVID‐19) infection reported in China in December 2019 has become a pandemic in a few weeks, affecting the entire world. In this respect, it is crucial to determine the case‐increase, case‐fatality, and case‐recovery rates to control COVID‐19. In this study, the case‐increase, case‐fatality, and case‐recovery rates of COVID‐19 in 36 European countries were analyzed with the meta‐analysis method using data released by the health organizations and WHO. The data were obtained from the website of health organizations of 36 European countries and the website of WHO until 11 May 2020. The analyses were carried out on 1 744 704 COVID‐19‐diagnosed cases in 36 European countries. The case‐increase, case‐fatality and case‐recovery rates of COVID‐19 were calculated using 95% confidence intervals (95% CI), single‐arm meta‐analysis, cross‐temporal meta‐analysis, and meta‐regression random‐effects model. The standardized case‐increase rate of COVID‐19 is 5% (95% CI [0.040, 0.063]) and the average case‐increase rate in European countries has started to decline by around 3% (95% CI [0.047, 0.083]) weekly. The countries with the highest rate of case increase are Belgium, Sweden, Russia, the Netherlands and the United Kingdom. Although the case‐fatality rate of COVID‐19 patients was 4.5% as of May 11 (95% CI [0.037‐0.055]), this rate is 6.3% (95% CI [0.047, 0.083]) in standardized time (6th week). The case‐recovery rates of patients are 46% (95% CI [0.376‐0.547]). This study presents important results regarding the COVID‐19 pandemic in Europe. Although the rate of increase in new COVID‐19 cases has dropped, there is not much decline in the case‐fatality rates and no increase in case‐recovery rates. The case‐fatality rate of COVID‐19 in Europe was estimated to be in the range of 4% to 4.5% and a minimum of 4 weeks (as of 11 May) is expected to have the figure below 1% in a country with an average case‐increase rate. Monitoring case fatalities in Belgium, the Netherlands and Sweden, and treatment successes in Germany and Austria play a role of utmost importance.

negative: Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020 Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717-459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250-67,632) patients requiring intensive care. Aggressive containment strategies are required.

negative: COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach BACKGROUND: The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. METHODS: In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. RESULTS: After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. DISCUSSION: This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.

negative: Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

negative: Pneumonie virale sévère de l'immunocompétent Résumé Les infections virales respiratoires communautaires sont fréquentes et le plus souvent bénignes. Beaucoup d'agents différents comme les virus influenza, ou para-influenza, le virus respiratoire syncitial, les rhinovirus, coronavirus, adénovirus et les herpès virus peuvent être isolés chez les patients immunocompétents. Parmi ces virus, le cytomégalovirus (CMV) peut être responsable de pneumonie nosocomiale en réanimation. Le diagnostic des infections virales est difficile car les signes cliniques sont non spécifiques et l'isolement du virus responsable difficile. Cependant, une symptomatologie clinique associant fièvre, myalgies, céphalées, pharyngite est fréquente dans les infections à Inflenza qui peuvent aboutir à des tableaux sévères. Enfin, le virus plus récent responsable d'infection respiratoire est un virus nouvellement découvert de la famille des coronavirus, le SRAS-CoV qui a été responsable d'une épidémie d'infections respiratoires sévères. Les pneumonies virales sont fréquentes mais probablement non diagnostiquées chez les patients immunocompétents. Cependant le diagnostic est nécessaire car pour la plupart des pathogènes il existe un traitement efficace. Le diagnostic repose sur l'histologie mais de nouvelles techniques comme la PCR doivent devenir d'utilisation courante pour améliorer le rendement diagnostique. Abstract Respiratory infections are frequently encountered in the community; these infections are usually associated with only minor consequences. Many different agents, such as influenza and parainfluenza virus, respiratory syncitial virus, rhinovirus, coronavirus, adenovirus and herpes virus can be found in immuno-competent patients. Among these pathogens, cytomegalovirus (CMV) has been found to be responsible for nosocomial pneumonia in ICU. The main problem for viral infections, is the diagnosis, isolation of the pathogen is often difficult and not always reliable and the symptoms not specific. However, influenza is characterised by fever, myalgia, headache and pharyngitis, this infection may be very mild, even asymptomatic, moderate or very severe. Finally, the most recent viral pathogen involved in respiratory disease is a newly discovered coronavirus, the SARS-CoV which was responsible for the worldwide outbreak of Severe Acute Respiratory Syndrome. Viral pneumonia is a common pathology which is probably underdiagnosed in immuno-competent patients; many reports show that even if the diagnosis is difficult to obtain, it is not useless as long as we have, for most of the pathogens, an effective treatment. The gold standard was histology, new techniques like PCR can probably make a difference and should be included in the guidelines to improve diagnostic efficiency.

negative: Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan Abstract Background In December 2019, COVID-19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. Objective The severity on admission, complications, treatment, and outcomes of COVID-19 patients were evaluated. Methods Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. Results We identified 269 (49.1%) of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-a), and high LDH level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in COVID-19 patients was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. Conclusions Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have high risk of death.

negative: The urgent need for integrated science to fight COVID-19 pandemic and beyond The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world’s scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics.

negative: Seven recommendations to rescue the patients and reduce the mortality from COVID-19 infection: An immunological point of view Now COVID-19 is causing a severe public health emergency and the mortality is rapidly increasing all over the world. In the current pandemic era, although there have been many efforts to diagnose a number of patients with symptoms or close contacts, there is no definite guideline for the initial therapeutic approach for them and therefore, many patients have been dying due to a hyperinflammatory immunological reaction labeled as “cytokine storm”. Severe patients are hospitalized and the treatment is done, though they have not been established yet. Currently, however, no treatment is provided for those who are isolated at home or shelter until they get severe symptoms, which will increase the harms to the patients. In this review, we discuss some important points dedicated to the management of patients with COVID-19, which should help reducing morbidity and mortality. In this era, we suggest 7 recommendations to rescue the patients and to reduce the morbidity and mortality due to COVID-19 based on the immunological point of view.

negative: COVID 19 et cancer : quelles sont les conséquences de la réorganisation des soins oncologiques?

negative: COVID-19 infection during pregnancy: A systematic review to summarize possible symptoms, treatments, and pregnancy outcomes Abstract Background: With the exponential increase in coronavirus disease 2019 (COVID-19) worldwide, an increasing proportion of pregnant women are now infected during their pregnancy. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during their pregnancy. Methods: Four databases (Medline, Web of Science, Scopus, and CINAHL) were searched on March 25, 2020, using the following keywords: 'COVID-19', 'nCoV-2019', and 'coronavirus'. Articles included if they reported either the symptoms, treatments for the women who had been infected with the COVID-19 during their pregnancy or pregnancy outcomes. The selected articles' results were summarized employing a narrative synthesis approach. Results: A total of nine studies were selected for this study, comprising 101 infected pregnant women. Other than the infected general population, infected pregnant women reported different symptoms; however, fever (66.7%), cough (39.4%), fatigue (15.2%), and breathing difficulties (14.1%) were common. Infected pregnant women were given different treatments than the general infected population. The C-section was a common (83.9%) mode of delivery among infected pregnant women, and a higher proportion of births were preterm births (30.4%) and low birth weight (17.9%). Conclusions: Pregnant infected women had different symptoms, and they were given dissimilar treatments than the general infected population. Healthcare providers may have appropriately informed about these symptoms and treatments. They, therefore, would be able to handle infection during pregnancy effectively, which would reduce common adverse consequences among infected pregnant women.

negative: Covid-19 related hospital admissions in the United States: needs and outcomes.

negative: Cranial Neuropathies and COVID-19: Neurotropism and Autoimmunity The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or "COVID-19" global pandemic began in late 2019. Like its predecessors, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), COVID-19 binds to angiotension converting enzyme 2 (ACE2) receptors to facilitate tissue invasion, and potentially gain entry into the nervous system.1 This single-stranded RNA virus shares 75-80% identical genome sequence with MERS-CoV and SARS-CoV, but has increased virulence, persistence, and lethality.2 Amid catastrophic human suffering, severe neurological complications of COVID-19 have been identified; yet, subtle neurological manifestations have likely been under-reported.

negative: Power of Artificial Intelligence to Diagnose and Prevent Further COVID-19 Outbreak: A Short Communication Novel coronavirus-19 (2019-nCoV or COVID-19) is by far the most dangerous coronavirus ever identified for the third time in the three decades capable of infecting not only the animals but also the humans across the globe. Nearly 6000 deaths have been recorded due mainly to COVID-19 outbreak worldwide and more than 50% of these deaths appeared to have evolved from China where the virus was thought to originate. The endemicity of COVID-19 dramatically surpassed severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) that were so far discovered in 2003 and 2012 respectively. Thus, the World Health Organization (WHO) has declared the 2019-nCoV outbreak not only a public health emergency but also pandemic in nature. Currently, over 120 countries including Nigeria were reported to have more than 157,844 confirmed cases and 5,846 deaths due mainly to COVID-19 outbreak as of March 15, 2020, 10:55 GMT. Artificial Intelligence (AI) is widely used to aid in the prediction, detection, response, recovery of disease and making clinical diagnosis. In this study, we highlighted the power of AI in the containment and mitigation of the spread of COVID-19 outbreak in African countries such as Nigeria where human to human contact is apparently inevitable.

negative: Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review Background: Coronavirus pandemic is currently a global public health emergency. At present, no pharmacological treatment is known to treat this condition, and there is a need to review the available treatments. Objective: While there have been studies to describe the role of chloroquine and hydroxychloroquine in various viral conditions, there is limited information about the use of them in COVID-19. This systematic review aims to summarize the available evidence regarding the role of chloroquine in treating coronavirus infection. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search was performed using PUBMED & Google Scholar to find articles about the role of CQ in COVID-19 patients. Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review. All the articles mentioned about the role of chloroquine and /or hydroxychloroquine in limiting the infection with SARS-CoV-2 (the virus causing COVID-19). Conclusions: There is theoretical, experimental, preclinical and clinical evidence of the effectiveness of chloroquine in patients affected with COVID-19. There is adequate evidence of drug safety from the long-time clinical use of chloroquine and hydroxychloroquine in other indications. More data from ongoing and future trials will add more insight into the role of chloroquine and hydroxychloroquine in COVID-19 infection.

negative: Evidence from internet search data shows information-seeking responses to news of local COVID-19 cases The COVID-19 outbreak is a global pandemic with community circulation in many countries, including the United States, with confirmed cases in all states. The course of this pandemic will be shaped by how governments enact timely policies and disseminate information and by how the public reacts to policies and information. Here, we examine information-seeking responses to the first COVID-19 case public announcement in a state. Using an event study framework for all US states, we show that such news increases collective attention to the crisis right away. However, the elevated level of attention is short-lived, even though the initial announcements are followed by increasingly strong policy measures. Specifically, searches for “coronavirus” increased by about 36% (95% CI: 27 to 44%) on the day immediately after the first case announcement but decreased back to the baseline level in less than a week or two. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms, and hand sanitizer. On the other hand, searches for information regarding community-level policies (e.g., quarantine, school closures, testing) or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are representative of the study period being relatively early in the epidemic, and more-elaborate policy responses were not yet part of the public discourse. Further analysis should track evolving patterns of responses to subsequent flows of public information.

negative: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.

negative: EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN. Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.

negative: Extrapulmonary manifestations of COVID-19: Radiologic and clinical overview COVID-19 is principally a respiratory illness and pulmonary manifestations constitute main presentations of the disease. According to the reported studies, SARS-CoV-2 infection is not limited to the respiratory system and other organs can be also affected. Renal dysfunction, gastrointestinal complications, liver dysfunction, cardiac manifestations, mediastinal findings, neurological abnormalities, and hematological manifestations are among the reported extrapulmonary features. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to rapidly scale up the diagnostic capacity to detect COVID-19 and its complications. This paper focuses on the most common extrapulmonary manifestations in patients with COVID-19 pneumonia. Further studies are needed to elaborate and confirm the causative relationship between SARS-CoV-2 and the reported extrapulmonary manifestations of COVID-19.

negative: Collateral damage: the impact on cancer outcomes of the COVID-19pandemic Background: Cancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival. Methods: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations. Findings: Per year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of six months would cause attributable death of 10,555 of these individuals with loss of 205,024 life years. For cancer surgery, average life years gained (LYGs) per patient are 18.1 under standard conditions and 15.9 with a delay of six months (a loss of 2.3 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2.25 resource-adjusted life years gained (RALYGs) under standard conditions and 1.98 RALYGs following delay of six months. For 94,912 hospital COVID-19 admissions, there are 474,505 LYGs requiring of 1,097,937 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.0 LYG and 0.43 RALYGs. Interpretation: Delay of six months in surgery for incident cancers would mitigate 43% of life years gained by hospitalisation of an equivalent volume of admissions for community acquired COVID-19. This rises to 62% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued. Funding: Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR)

negative: Effect of COVID‐19 in selecting otolaryngology as a specialty Coronavirus disease 2019 has undoubtedly impacted the health care system while causing lasting and profound implications for medical education. Senior medical students seeking exposure to the field of otolaryngology now find themselves in the challenging position of obtaining the experiences to make an informed decision on a future specialty. Virtual electives using comprehensive online material, discussion, and videos as well as the advent of telemedicine may be potential solutions to increase exposure to otolaryngology. While incorporating opportunities for authentic patient interactions is still a challenge, it is crucial that the academic otolaryngology community prioritize seeking solutions for interested medical students.

negative: Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation: protocol for a randomized controlled pilot study Background: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with no proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. Objective: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. Methods: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is the severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24 hours after initiation of treatment. Secondary outcomes include hospital and intensive care unit length of stay, duration of mechanical ventilation, amount of viral shedding, and 30-day mortality. Results: Resulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: pending. Conclusions: With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.

negative: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19 BACKGROUND: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. RESULTS: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. CONCLUSIONS: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. METHODS: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.

negative: Association of national Bacille Calmette-Guerin vaccination policy with COVID-19 epidemiology: an ecological study in 78 countries A possible association between national Bacille Calmette-Guerin (BCG) vaccination policy and lower COVID-19 incidence has been suggested in some preprint papers. Using publicly accessible databases, I explored associations of national BCG vaccination policy with COVID-19 epidemiology in 78 countries. Data collection was conducted from April 25 to May 5, 2020. I compared countries that have a current universal BCG vaccination policy (BCG countries), with countries that currently lack such a policy (non-BCG countries). The mixed effect model revealed national BCG policy decreases in the country-specific risk of death by COVID-19, correspond to odds ratio of 0.446 (95% confidence intervals 0.323 - 0.614, P =1x10-5). In BCG countries, the case increase rate was attenuated marginally by 25.4% (95% CI 3.0 to 42.7, P=0.029) as compared with those of the non-BCG countries. Although the protective mechanism of BCG vaccination against COVID-19 remains unknown, further laboratory and clinical research should be warranted.

negative: [Takotsubo syndrome during SARS-CoV-2 pneumonia: a possible cardiovascular complication]. Takotsubo syndrome (TTS) is one of the causes of myocardial infarction with non-obstructive coronary arteries, and is often triggered by physical events (e.g. acute respiratory failure), or emotional events (e.g. loss of a family member, cardiac stress induced by an acute illness). SARS-CoV-2 pneumonia currently represents a worldwide health problem; the correlations between cardiovascular disease, myocardial injury and SARS-CoV-2 infection are still unclear, but initial data show that myocardial damage represents a negative prognostic factor. Myocardial injury during SARS-CoV-2, as defined by a pathological rise in circulating troponin levels, is not an uncommon complication in hospitalized patients, and is significantly more frequent in intensive care unit patients and among those who died. In this setting, myocardial injury is mainly secondary to type 2 myocardial infarction (mismatch in myocardial oxygen supply and demand during respiratory failure); other causes include myocarditis, coronary thrombosis, sepsis or septic shock. At present, only few cases of TTS have been described during SARS-CoV-2. Here we report the case of a patient hospitalized for pneumonia and respiratory failure due to SARS-CoV-2 with subsequent onset of TTS triggered by both physical and emotional events.

negative: Clinical Outcomes of Metabolic Surgery: Microvascular and Macrovascular Complications. Understanding of the long-term clinical outcomes associated with bariatric surgery has recently been advanced. Research related to the sequelae of diabetes-in particular, long-term microvascular and macrovascular complications-in patients who undergo weight-loss surgery is imperative to this pursuit. While numerous randomized control trials have assessed glucose control with bariatric surgery compared with intensive medical therapy, bariatric surgery outcome data relating to microvascular and macrovascular complications have been limited to observational studies and nonrandomized clinical trials. As a result, whether bariatric surgery is associated with a long-term reduction in microvascular and macrovascular complications when compared with current intensive glycemic control therapy cannot be determined because the evidence is insufficient. However, the consistent salutary effects of bariatric surgery on diabetes remission and glycemic improvement support the opportunity (and need) to conduct high-quality studies of bariatric surgery versus intensive glucose control. This review provides relevant background information related to the treatment of diabetes, hyperglycemia, and long-term complications; reports clinical findings (to date) with bariatric surgery; and identifies ongoing research focusing on long-term vascular outcomes associated with bariatric surgery.

negative: COVID-19 in diabetic patients: related risks and specifics of management Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

negative: Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence Purpose: The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trial Registries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results: Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions: The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available. Keywords: Hydroxychloroquine, SARS-CoV-2, COVID-19, Corona virus, nCov2, systematic review

negative: COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.

negative: Impact of viral epidemic outbreaks on mental health of healthcare workers: a rapid systematic review Objectives: To examine the impact of providing healthcare during or after health emergencies caused by viral epidemic outbreaks on healthcare workers (HCWs) mental health, and to assess the available evidence base regarding interventions to reduce such impact. Design: Systematic rapid review and meta-analysis. Data sources: MEDLINE, Embase, and PsycINFO, searched up to 23 March 2020. Method: We selected observational and experimental studies examining the impact on mental health of epidemic outbreaks on HCWs. Titles and abstracts were screened by one reviewer, and full texts were evaluated by two reviewers independently. We extracted study characteristics, symptoms, prevalence of mental health problems, risk factors, mental health interventions, and its impact. We assessed risk of bias for each individual study. We conducted a narrative and tabulated synthesis of the results. We pooled data using random-effects meta-analyses to estimate the prevalence of specific mental health problems. We followed the GRADE approach to assess the certainty in the evidence. Results: We included 61 studies (56 examining impact on mental health and five about interventions to reduce such impact). Most were conducted in Asia (59%), examined the impact of the SARS epidemic (69%), and took place in the hospital setting (79%). The pooled prevalence was higher for anxiety (45%, 95% CI 21 to 69%; 6 studies, 3,373 participants), followed by depression (38%, 95% CI 15 to 60%; 7 studies, 3,636 participants), acute stress disorder (31%, 95% CI 0 to 82%, 3 studies , 2,587 participants), burnout (29%, 95% CI 25 to 32%; 3 studies; 1,168 participants) and post-traumatic stress disorder (19%, 95% CI 11 to 26%, 10 studies, 3,121 participants). Based on 37 studies, we identified a broad number of risk factors for these conditions, including sociodemographic: younger age and female gender; social factors: lack of social support, social rejection or isolation, stigmatization; and occupational: working in a high risk environment (frontline staff), specific occupational roles (e.g., nurse), and lower levels of specialized training, preparedness and job experience. Two out of five interventions identified were educational aimed to prevent mental health problems by increasing HCWs resilience. These interventions showed positive effects in confidence in support and training, pandemic self-efficacy and interpersonal problems solving (very low certainty). One multifaceted intervention (based on training and organisational changes) targeted at hospital nurses during the SARS epidemic produced statistically significant improvements in anxiety, depression, and sleep quality (very low certainty). The impact of the two remaining interventions (multifaceted and based on psychotherapy provision) was unreported. Conclusion: The prevalence of anxiety, depression, acute and post-traumatic stress disorder, and burnout, was high both during and after the outbreaks. These problems not only have a long-lasting effect on the mental health of HCWs, but also hinder the urgent response to the current COVID-19 pandemic, by jeopardising attention and decision-making. Governments and healthcare authorities should take urgent actions to protect the mental health of HCWs. In light of the limited evidence regarding the impact of interventions to tackle mental health problems in HCWs, the risk factors identified in this study represent important targets for future interventions.

negative: Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors Abstract Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups. Conclusion Dipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.

negative: Cardiac Surgery and the COVID-19 Pandemic: What We Know, What We Don’t Know, and What We Need to Do

negative: Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery. PURPOSE Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

negative: Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?/ Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?/ Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

negative: Short-Term Outcomes of Laparoscopic Total Gastrectomy Performed by a Single Surgeon Experienced in Open Gastrectomy: Review of Initial Experience. PURPOSE Laparoscopic total gastrectomy (LTG) is more complicated than laparoscopic distal gastrectomy, especially during a surgeon's initial experience with the technique. In this study, we evaluated the short-term outcomes of and learning curve for LTG during the initial cases of a single surgeon compared with those of open total gastrectomy (OTG). MATERIALS AND METHODS Between 2009 and 2013, 134 OTG and 74 LTG procedures were performed by a single surgeon who was experienced with OTG but new to performing LTG. Clinical characteristics, operative parameters, and short-term postoperative outcomes were compared between groups. RESULTS Advanced gastric cancer and D2 lymph node dissection were more common in the OTG than LTG group. Although the operation time was significantly longer for LTG than for OTG (175.7±43.1 minutes vs. 217.5±63.4 minutes), LTG seems to be slightly superior or similar to OTG in terms of postoperative recovery measures. The operation time moving average of 15 cases in the LTG group decreased gradually, and the curve flattened at 54 cases. The postoperative complication rate was similar for the two groups (11.9% vs. 13.5%). No anastomotic or stump leaks occurred. CONCLUSIONS Although LTG is technically difficult and operation time is longer for surgeons experienced in open surgery, it can be performed safely, even during a surgeon's early experience with the technique. Considering the benefits of minimally invasive surgery, LTG is recommended for early gastric cancer.

negative: U.S. county-level characteristics to inform equitable COVID-19 response BACKGROUND: The spread of Coronavirus Disease 2019 (COVID-19) across the United States confirms that not all Americans are equally at risk of infection, severe disease, or mortality. A range of intersecting biological, demographic, and socioeconomic factors are likely to determine an individual’s susceptibility to COVID-19. These factors vary significantly across counties in the United States, and often reflect the structural inequities in our society. Recognizing this vast inter-county variation in risks will be critical to mounting an adequate response strategy. METHODS AND FINDINGS: Using publicly available county-specific data we identified key biological, demographic, and socioeconomic factors influencing susceptibility to COVID-19, guided by international experiences and consideration of epidemiological parameters of importance. We created bivariate county-level maps to summarize examples of key relationships across these categories, grouping age and poverty; comorbidities and lack of health insurance; proximity, density and bed capacity; and race and ethnicity, and premature death. We have also made available an interactive online tool that allows public health officials to query risk factors most relevant to their local context. Our data demonstrate significant inter-county variation in key epidemiological risk factors, with a clustering of counties in certain states, which will result in an increased demand on their public health system. While the East and West coast cities are particularly vulnerable owing to their densities (and travel routes), a large number of counties in the Southeastern states have a high proportion of at-risk populations, with high levels of poverty, comorbidities, and premature death at baseline, and low levels of health insurance coverage. The list of variables we have examined is by no means comprehensive, and several of them are interrelated and magnify underlying vulnerabilities. The online tool allows readers to explore additional combinations of risk factors, set categorical thresholds for each covariate, and filter counties above different population thresholds. CONCLUSION: COVID-19 responses and decision making in the United States remain decentralized. Both the federal and state governments will benefit from recognizing high intra-state, inter-county variation in population risks and response capacity. Many of the factors that are likely to exacerbate the burden of COVID-19 and the demand on healthcare systems are the compounded result of long-standing structural inequalities in US society. Strategies to protect those in the most vulnerable counties will require urgent measures to better support communities’ attempts at social distancing and to accelerate cooperation across jurisdictions to supply personnel and equipment to counties that will experience high demand.

negative: Coronavirus Disease 2019 (COVID-19) and its implications for cardiovascular care: expert document from the German Cardiac Society and the World Heart Federation Coronavirus diseases 2019 (COVID-19) has become a worldwide pandemic affecting people at high risk and particularly at advanced age, cardiovascular and pulmonary disease. As cardiovascular patients are at high risk but also have dyspnea and fatigue as leading symptoms, prevention, diagnostics and treatment in these patients are important to provide adequate care for those with or without COVID-19 but most importantly when comorbid cardiovascular conditions are present. Severe COVID-19 with acute respiratory distress (ARDS) is challenging as patients with elevated myocardial markers such as troponin are at enhanced high risk for fatal outcomes. As angiotensin-converting enzyme 2 (ACE2) is regarded as the viral receptor for cell entry and as the Coronavirus is downregulating this enzyme, which provides cardiovascular and pulmonary protection, there is ongoing discussions on whether treatment with cardiovascular drugs, which upregulate the viral receptor ACE2 should be modified. As most of the COVID-19 patients have cardiovascular comorbidities like hypertension, diabetes, coronary artery disease and heart failure, which imposes a high risk on these patients, cardiovascular therapy should not be modified or even withdrawn. As cardiac injury is a common feature of COVID-19 associated ARDS and is linked with poor outcomes, swift diagnostic management and specialist care of cardiovascular patients in the area of COVID-19 is of particular importance and deserves special attention.

negative: COVID-19 Trends and Forecast in the Eastern Mediterranean Region With a Particular Focus on Pakistan First reported in China, the coronavirus responsible for coronavirus disease 2019 (COVID-19) has spread to 213 countries and territories around the world as of April 26, 2020. This study was designed to explore COVID-19 trends in the Eastern Mediterranean Region (EMR), with a particular focus on Pakistan. Daily reports and updates from the Ministry of National Health Services Regulations and Coordination COVID-19 Pakistan and the European Centre for Disease Prevention and Control were collected and study-specific data were extracted and analyzed. Our analysis revealed that, as of April 26, 2020, a total of 22 countries and territories in the EMR have reported COVID-19 cases. Iran had the highest number of cases (89,329) followed by Saudi Arabia (16,299), Pakistan (12,723), and the United Arab Emirates (9,813). Egypt (7.1%), Iran (6.3%), and Iraq (4.9%) had high case fatality rates; Lebanon (3.4%) and Pakistan (2.1%) had moderate case fatality rates; Saudi Arabia and the United Arab Emirates had low case fatality rates of 0.8% and 0.7%, respectively. Iran (76.3%) and Iraq (69.4 %) had the highest recovery rate followed by Pakistan (22.5%), the United Arab Emirates (19.2%), and Saudi Arabia (13.6%). If the current trend continues, based on the susceptible, infected, recovered (SIR) epidemiological model, we predict that EMR countries might experience a surge in the number of COVID-19 cases, resulting in as many as 2.12 million cases in Iran, 0.58 million in Saudi Arabia, and 0.51 million in Pakistan by June 20, 2020. Pakistan is the most populated country in the EMR and was the third most-affected country in terms of the number of cases with moderate case fatality and recovery rates. We predict that Pakistan’s weak healthcare system would not be able to sustain care if there is an explosive increase in the number of cases due to insufficient and inconsistent disease prevention and control policies. The best strategy for mitigating the COVID-19 pandemic is to strictly follow recommendations based on epidemiological principles.

negative: Neurological manifestations and implications of COVID-19 pandemic The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.

negative: Estimates of the severity of COVID-19 disease Background: A range of case fatality ratio (CFR) estimates for COVID 19 have been produced that differ substantially in magnitude. Methods: We used individual-case data from mainland China and cases detected outside mainland China to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the CFR by relating the aggregate distribution of cases by dates of onset to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for the demography of the population, and age and location-based under ascertainment. We additionally estimated the CFR from individual linelist data on 1,334 cases identified outside mainland China. We used data on the PCR prevalence in international residents repatriated from China at the end of January 2020 to obtain age-stratified estimates of the infection fatality ratio (IFR). Using data on age stratified severity in a subset of 3,665 cases from China, we estimated the proportion of infections that will likely require hospitalisation. Findings: We estimate the mean duration from onset-of-symptoms to death to be 17.8 days (95% credible interval, crI 16.9,19.2 days) and from onset-of-symptoms to hospital discharge to be 22.6 days (95% crI 21.1,24.4 days). We estimate a crude CFR of 3.67% (95% crI 3.56%,3.80%) in cases from mainland China. Adjusting for demography and under-ascertainment of milder cases in Wuhan relative to the rest of China, we obtain a best estimate of the CFR in China of 1.38% (95% crI 1.23%,1.53%) with substantially higher values in older ages. Our estimate of the CFR from international cases stratified by age (under 60 or 60 and above) are consistent with these estimates from China. We obtain an overall IFR estimate for China of 0.66% (0.39%,1.33%), again with an increasing profile with age. Interpretation: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.

negative: Practical recommendations for the management of diabetes in patients with COVID-19 Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.

negative: Trends and Prediction in Daily New Cases and Deaths of COVID-19 in the United States: An Internet Search-Interest Based Model BACKGROUND AND OBJECTIVES: The daily incidence and deaths of coronavirus disease 2019 (COVID-19) in the USA are poorly understood. Internet search interest was found to be correlated with COVID-19 daily incidence in China, but has not yet been applied to the USA. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the USA. METHODS: We extracted COVID-19 daily new cases and deaths in the USA from two population-based datasets, namely 1-point-3-acres.com and the Johns Hopkins COVID-19 data repository. The internet search-interest of COVID-19-related terms was obtained using Google Trends. The Pearson correlation test and general linear model were used to examine correlations and predict trends, respectively. RESULTS: There were 636,282 new cases and,325 deaths of COVID-19 in the USA from March 1 to April 15, 2020, with a crude mortality of 4.45%. The daily new cases peaked at 35,098 cases on April 10, 2020 and the daily deaths peaked at 2,494 on April 15, 2020. The search interest of COVID, “COVID pneumonia” and “COVID heart” were correlated with COVID-19 daily incidence, with 12 or 14 days of delay (Pearson’s r = 0.978, 0.978 and 0.979, respectively) and deaths with 19 days of delay (Pearson’s r = 0.963, 0.958 and 0.970, respectively). The 7-day follow-up with prospectively collected data showed no significant correlations of the observed data with the predicted daily new cases or daily deaths, using search interest of COVID, COVID heart, and COVID pneumonia. CONCLUSIONS: Search terms related to COVID-19 are highly correlated with the COVID-19 daily new cases and deaths in the USA.

negative: Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults RAPID COMMUNICATION 22 March 2020 Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Background: The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods: Using population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged ≥30 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings: 20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged ≤70 years with ≥1 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of ≥2 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with ≥3 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population (do-nothing), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. Interpretation: We provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected (do nothing) scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.

negative: Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.

negative: A close-up on COVID-19 and cardiovascular diseases Abstract Aims To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. Data Synthesis COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia and stress response et al, all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. Conclusions In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis. The pandemic of COVID-19 has been taking lives worldwide. It caused by a novel coronavirus which human being are lack of defensive function in whole population. It targets human’s lung and causes serious damage of lungs. Based on early reports, for people with underlying heart issues, the concerns are serious. It appears people over 65 with coronary heart diseases or hypertension is more likely to be infected and to develop more severe symptoms. In addition, some of hospitalized COVID-19 patients had cardiovascular diseases in China. As characteristic analysis of COVID-19 patients, hypertension and severe myocardial damage contribute to severity [1] and mortality of COVID-19 patients [2]. Therefore, to better understand the development of COVID-19 and the impacts of cardiovascular diseases will add valuable measures to the management of COVID-19 patients.

negative: Forecasting the Peak of Novel Coronavirus Disease in Egypt Using Current Confirmed Cases and Deaths The first case of coronavirus disease 2019 (COVID-19) in Egypt was reported on 14 February 2020 and the number of reported cases has increased daily. The purpose of this study is to describe the current situation of Covid-19 in Egypt and to predict the expected timing of the peak of this epidemic using current confirmed cases and deaths. We used one of the online tools; the Epidemic Calculator that utilizes, the well-known SEIR compartmental model. We utilized the daily reports published by the Egyptian Ministry of Health & Population from 14 February to 11 May 2020. Given the highest calculated case fatality rate (7.7%), the number of hospitalized individuals is expected to peak in the middle of June with a peak of hospitalized cases of 20,126 individuals and total expected deaths 12,303. We recommend strengthening of the Egyptian preventive and control measures so as to decrease the CFR and the number of cases to the least possible as we approach the epidemic peak. It is most important that appropriate quarantine measures are retained., the quarantine measures should not be relaxed before the end of June, 2020.

negative: Urban Air Pollution May Enhance COVID-19 Case-Fatality and Mortality Rates in the United States BACKGROUND: The novel human coronavirus disease 2019 (COVID-19) pandemic has claimed more than 240,000 lives worldwide, causing tremendous public health, social, and economic damages. While the risk factors of COVID-19 are still under investigation, environmental factors, such as urban air pollution, may play an important role in increasing population susceptibility to COVID-19 pathogenesis. METHODS: We conducted a cross-sectional nationwide study using zero-inflated negative binomial models to estimate the association between long-term (2010–2016) county-level exposures to NO(2), PM(2.5) and O(3) and county-level COVID-19 case-fatality and mortality rates in the US. We used both single and multipollutant models and controlled for spatial trends and a comprehensive set of potential confounders, including state-level test positive rate, county-level healthcare capacity, phase-of-epidemic, population mobility, sociodemographic, socioeconomic status, behavior risk factors, and meteorological factors. RESULTS: 1,027,799 COVID-19 cases and 58,489 deaths were reported in 3,122 US counties from January 22, 2020 to April 29, 2020, with an overall observed case-fatality rate of 5.8%. Spatial variations were observed for both COVID-19 death outcomes and long-term ambient air pollutant levels. County-level average NO(2) concentrations were positively associated with both COVID-19 case-fatality rate and mortality rate in single-, bi-, and tri-pollutant models (p-values<0.05). Per inter-quartile range (IQR) increase in NO(2) (4.6 ppb), COVID-19 case-fatality rate and mortality rate were associated with an increase of 7.1% (95% CI 1.2% to 13.4%) and 11.2% (95% CI 3.4% to 19.5%), respectively. We did not observe significant associations between long-term exposures to PM(2.5) or O(3) and COVID-19 death outcomes (p-values>0.05), although per IQR increase in PM(2.5) (3.4 ug/m(3)) was marginally associated with 10.8% (95% CI: −1.1% to 24.1%) increase in COVID-19 mortality rate. DISCUSSIONS AND CONCLUSIONS: Long-term exposure to NO(2), which largely arises from urban combustion sources such as traffic, may enhance susceptibility to severe COVID-19 outcomes, independent of long-term PM(2.5) and O(3) exposure. The results support targeted public health actions to protect residents from COVID-19 in heavily polluted regions with historically high NO(2) levels. Moreover, continuation of current efforts to lower traffic emissions and ambient air pollution levels may be an important component of reducing population-level risk of COVID-19 deaths.

negative: Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial Background No clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19). Methods We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days. Results 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014). Conclusions Among patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).

negative: Strategies for Managing the Impacts of Disruptions During COVID-19: an Example of Toilet Paper Due to the recent pandemic of coronavirus, known as the COVID-19 outbreak, the supply chains have been impacted most significantly. Manufacturers of certain items have experienced a substantial increase in demand, and on the other hand, raw materials supply, to produce those items, has reduced because of supply failure. To overcome these challenges, this paper proposes some strategies to improve service level during an extraordinary pandemic outbreak, such as COVID-19, for the most wanted products such as toilet paper. This study considers meeting the increased demand of the customers for an essential product of daily life like toilet paper during a pandemic is beyond the traditional economic objective, i.e., increase profit, of the manufacturers. Instead, this should be more about the social responsibility of all the manufactures to ensure that they can serve more customers. Motivated by this and taking toilet paper as an example of the product, we first analyzed the current scenario of the manufacturing and the demand for the product and then proposed some strategies to deal with this unprecedented risk and analyzed the results. We have compared the results, using hypothetical data, between the current scenario and proposed strategies. The result shows that sharing information and resources from all manufacturers to produce under a single brand, emergency sourcing, producing basic quality items, and packing in the smallest sizes have a significant positive impact on the service level. This paper first investigates the strategies for a high-demand and essential item during a pandemic situation and proposes strategies to deal with this unique, extraordinary disruption.

negative: Understanding the CoVID-19 pandemic Curve through statistical approach Current research is an attempt to understand the CoVID-19 pandemic curve through statistical approach of probability density function with associated skewness and kurtosis measures, change point detection and polynomial fitting to estimate infected population along with 30 days projection. The pandemic curve has been explored for above average affected countries, six regions and global scale during 64 days of 22nd January to 24th March, 2020. The global cases infection as well as recovery rate curves remained in the ranged of 0 - 9.89 and 0 - 8.89%, respectively. The confirmed cases probability density curve is high positive skewed and leptokurtic with mean global infected daily population of 6620. The recovered cases showed bimodal positive skewed curve of leptokurtic type with daily recovery of 1708. The change point detection helped to understand the CoVID-19 curve in term of sudden change in term of mean or mean with variance. This pointed out disease curve is consist of three phases and last segment that varies in term of day lengths. The mean with variance based change detection is better in differentiating phases and associated segment length as compared to mean. Global infected population might rise in the range of 0.750 to 4.680 million by 24th April 2020, depending upon the pandemic curve progress beyond 24th March, 2020. Expected most affected countries will be USA, Italy, China, Spain, Germany, France, Switzerland, Iran and UK with at least infected population of over 0.100 million. Infected population polynomial projection errors remained in the range of -78.8 to 49.0%.

negative: 1-Year Pulmonary Function and Health Status in Survivors of Severe Acute Respiratory Syndrome Study objectives To characterize the long-term pulmonary function and health status in a prospectively identified cohort of patients who survived the severe acute respiratory syndrome (SARS). Design Prospective follow-up cohort study. Setting University-affiliated hospital. Patients Ninety-four patients who recovered from SARS were assessed at a uniform time point of 1 year after hospital discharge. Measurements The study included the measurement of static and dynamic lung volumes, the determination of the diffusing capacity of the lung for carbon monoxide (Dlco), and a health status evaluation using the St. George Respiratory Questionnaire (SGRQ). Results Eleven patients (12%) had mild impairment of FVC, 20 (21%) had mild impairment of FEV1, 5 (5%) had mild impairment of the FEV1/FVC ratio, and 17 (18%) had mild impairment of the Dlco. There was one patient (1%) who had moderate impairment of FVC, one patient (1%) who had moderate impairment of the FEV1/FVC ratio, and three patients (3%) who had moderate impairment of the Dlco. No pulmonary function abnormalities were detected in 59 patients (63%). Mean scores were significantly higher (ie, worse) than the population norms in the activity (p < 0.001), impacts (p < 0.001), and total (p < 0.001) domains of the SGRQ. Conclusions One year after recovery from SARS, persistent pulmonary function impairment was found in about one third of patients. The health status of SARS survivors was also significantly worse compared with the healthy population. The main determinants of morbidity in recovered SARS patients need to be further defined.

negative: Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05164-x) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.

negative: ReCOVery: A Multimodal Repository for COVID-19 News Credibility Research First identified in Wuhan, China, in December 2019, the outbreak of COVID-19 has been declared as a global emergency in January, and a pandemic in March 2020 by the World Health Organization (WHO). Along with this pandemic, we are also experiencing an"infodemic"of information with low credibility such as fake news and conspiracies. In this work, we present ReCOVery, a repository designed and constructed to facilitate the studies of combating such information regarding COVID-19. We first broadly search and investigate ~2,000 news publishers, from which 61 are identified with extreme [high or low] levels of credibility. By inheriting the credibility of the media on which they were published, a total of 2,029 news articles on coronavirus, published from January to May 2020, are collected in the repository, along with 140,820 tweets that reveal how these news articles are spread on the social network. The repository provides multimodal information of news articles on coronavirus, including textual, visual, temporal, and network information. The way that news credibility is obtained allows a trade-off between dataset scalability and label accuracy. Extensive experiments are conducted to present data statistics and distributions, as well as to provide baseline performances for predicting news credibility so that future methods can be directly compared. Our repository is available at http://coronavirus-fakenews.com, which will be timely updated.

negative: A Case Series of Recurrent Viral RNA Positivity in Recovered COVID-19 Chinese Patients

negative: Prediction of the COVID-19 Epidemic Trends Based on SEIR and AI Models The outbreak of novel coronavirus-caused pneumonia (COVID-19) in Wuhan has attracted worldwide attention. To contain its spread, China adopted unprecedented nationwide interventions on January 23. We sought to show how these control measures impacted the containment of the epidemic. We proposed an SEIR(Susceptible-Exposed- Infectious-Removed) model to analyze the epidemic trend in Wuhan and use the AI model to analyze the epidemic trend in non-Wuhan areas. We found that if the closure was lifted, the outbreak in non-Wuhan areas of mainland China would double in size. Our SEIR and AI model was effective in predicting the COVID-19 epidemic peaks and sizes. The implementation of control measures on January 23, 2020, was indispensable in reducing the eventual COVID-19 epidemic size.

negative: Coronavirus Disease (COVID-19) and Traumatic Stress: Probable Risk Factors and Correlates of Posttraumatic Stress Disorder The Coronavirus Disease (COVID-19) outbreak, which first began in December 2019 in China, has since become a global health crisis with vast and devastating consequences for individuals and societies. Both earlier research and recent findings suggest that infectious disease epidemics and pandemics can be highly traumatic experiences for some individuals and lead to posttraumatic stress disorder (PTSD) and chronic psychological distress. Mental health risks associated with COVID-19 have yet to be systematically studied; however, the emerging literature on COVID-19, as well as previous studies on infectious disease outbreaks provide insights into probable risk factors and correlates of PTSD. In this paper, we provide a brief review of these studies and discuss probable risk factors for PTSD and chronic psychological distress related to COVID-19.

negative: COVID-19: What Should Interventional Radiologists Know and What Can They Do? The outbreak of coronavirus disease 2019 (COVID-19) in late December 2019 in Wuhan, China, has been characterized as a “pandemic” by the World Health Organization and has resulted in 81,603 confirmed cases in China, among the 334,981 cases confirmed in 189 countries as of 09:00 am, March 24, 2020 (China central standard time). During the past 3 months, hundreds of thousands of Chinese health care workers, including interventional radiologists (IRs), have been fighting this battle against the horrifying COVID-19 disease. As IRs, what should we know and what can we do when facing this challenge? This paper shares the experience we have gone through.

negative: Recovery Ratios Reliably Anticipate COVID-19 Pandemic Progression The COVID-19 pandemic is placing unprecedented demands on healthcare systems worldwide and exacting a massive humanitarian toll. This makes the development of accurate predictive models imperative, not just for understanding the course of the pandemic but more importantly for gaining insight into the efficacy of public health measures and planning accordingly. Epidemiological models are forced to make assumptions about many unknowns and therefore can be unreliable. Here, taking an empirical approach, we report a 20-30 day lag between the peak of confirmed to recovered cases and the peak of daily deaths in each country, independent of the epoch of that country in its pandemic cycle. This analysis is expected to be largely independent of the proportion of the population being tested and therefore should aid in planning around the timing and easing of public health measures. Our data also suggests broad predictions for the number of fatalities, generally somewhat lower than most other models. Finally, our model suggests that the world as a whole is shortly to enter a recovery phase, at least as far as the first pandemic wave is concerned.

negative: Evaluation of eluents for the recovery of an enveloped virus from hands by whole-hand sampling AIMS: The objective of this research is to evaluate eluents for recovery of an enveloped bacteriophage, Φ6, using whole-hand sampling. METHODS AND RESULTS: Virus was applied to the hands of volunteers and sampled by the glove juice method with 1.5% beef extract (BE), phosphate buffered saline (PBS), 0.01 and 0.1% Tween 80, tryptic soy broth (TSB), and 9% NaCl. Each volunteer underwent multiple rounds application and hand sampling. Mean log(10) virus loss across trials was 2.6 for BE, 2.8 for PBS, 2.4 for TSB, 3.8 for NaCl, 3.0 for 0.1% Tween 80, and 2.9 for 0.01% Tween 80. Within each volunteer, there was a decline in viral loss from the first to last trial. CONCLUSIONS: These eluents can recover Φ6 from hands with ~2-3 log(10) loss, comparable to recoveries previously reported for influenza. Protein and detergent-based eluents may have similar recoveries, but recovery may still vary across repeated sampling. SIGNIFICANCE AND IMPACT: Based on current work, protein-based eluents such as beef extract can maximize recovery of enveloped viruses during hand sampling, providing methods for evaluating survival and transmission of enveloped viruses on hands. Further exploration is needed of the effect of repeated sampling on recovery from whole-hand sampling.

negative: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

negative: “Challenges for liver transplantation during recovery from the COVID-19 pandemic: insights and recommendations” Abstract The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many liver transplant (LT) services worldwide dropped down or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of liver transplants are likely to drop in the immediate post-COVID era. Prolong, and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients as well as members in transplant teams. LT programs may have to revise the existing strategies in selecting donors and recipients for transplants. Re-designing service provision, restructuring of outpatient care, careful screening and selection of donors and recipient, performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services are to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling. This paper discusses the different elements affecting and the widespread impact of COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the healthcare needs during this pandemic and beyond.

negative: Quelle conduite à tenir pour le suivi des patients glaucomateux en cette période d'épidémie de Covid-19 à virus SARS-CoV-2 ?/ [How to approach follow-up of glaucoma patients during COVID-19 pandemic]

negative: COVID-19 follow-up planning: what will we be missing? There is a real need for a discharge plan for COVID-19 survivors in the UK. Follow-up imaging could help assess the resolution of infection, exclude underlying malignancy and identify post-inflammatory fibrosis. https://bit.ly/2YJ8hyg

negative: Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study Background The ongoing epidemics of coronavirus disease 2019 (COVID-19) have caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. Methods We conducted a case-control study to compare clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. Results During January 24 to February 29, 2020, there were sixteen pregnant women with confirmed COVID-19 pneumonia and eighteen suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest took cesarean section. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest CT images of COVID-19 pneumonia. Compared to the controls, COVID-19 pneumonia patients had lower counts of white blood cells (WBC), neutrophils, C-reactive protein (CRP), and alanine aminotransferase (ALT) on admission. Increased levels of WBC, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. There were three (18.8%) and two (10.5%) of the mothers with confirmed or suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than the control group. None experienced respiratory failure during hospital stay. COVID-19 infection was not found in the newborns and none developed severe neonatal complications. Conclusion Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal delivery or caesarean section. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

negative: Clinical Features of COVID-19-Related Liver Functional Abnormality BACKGROUND & AIMS: Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. METHODS: We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. RESULTS: Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021). CONCLUSIONS: More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

negative: The important role of polysaccharides from a traditional Chinese medicine-Lung Cleansing and Detoxifying Decoction against the COVID-19 pandemic Abstract The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application.

negative: Encephalitis Associated with COVID-19 Infection in an 11 Year-Old Child

negative: Metronomic oral vinorelbine and lung cancer therapy during the COVID 19 pandemic: a single-center experience • Intravenous vinorelbine is a standard treatment for advanced NSCLC; • Oral vinorelbine is equally effective as compared to intravenous vinorelbine; • Metronomic oral formulation of vinorelbine is a safe and active treatment for advanced NSCLC; • No established treatment is a “gold standard” during COVID19 era; • Metronomic oral vinorelbine permitted to carry on active treatment during COVID Emergency; • Metronomic oral vinorelbine reduce side effects and hospital visits to lung cancer patients; • Management of lung cancer patients may be improved by metronomic oral vinorelbine.

negative: Novel Coronavirus Disease (COVID-19) and Biologic Therapy for Psoriasis: Successful Recovery in Two Patients After Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) The outbreak of the novel coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing COVID-19 was first reported in late December 2019. Many patients with psoriasis on biologic therapy have asked their medical providers about the effect of biologics on COVID-19. However, it is currently unknown how biologic therapy for psoriasis might impact patients with psoriasis and COVID-19. In this article, we report on the clinical course of two patients on biologic medication for psoriasis who developed COVID-19 and successfully recovered from SARS-CoV-2 infection. Both patients presented with fever and respiratory symptoms, but neither patient required hospitalization. While more research is needed, it is reassuring to know that successful recovery is possible after COVID-19 infection in patients on biologic therapy for psoriasis.

negative: Cancer patients and research during COVID-19 pandemic: A systematic review of current evidence Abstract The novel coronavirus, also known as SARS-Cov-2 or COVID-19 has become a worldwide threat and the major healthcare concern of the year 2020. Cancer research was directly affected by the emerging of this disease. According to some Chinese studies, cancer patients are more vulnerable to COVID-19 complications. This observation led many oncologists to change their daily practice in cancer care, without solid evidence and recommendations. Moreover, the COVID-19 manifestations as well as its diagnosis are particular in this special population. In this review paper we expose the challenges of cancer management in the era of SARS-CoV-2, the epidemiological, clinical, pathological and radiological characteristics of the disease in cancer patients and its outcomes on this population. Finally, we focus on strategies that are followed in cancer management with review of national and international guidelines.

negative: Acute Disseminated Encephalomyelitis Associated With Influenza A H1N1 Infection Abstract Acute disseminated encephalomyelitis is an immune-mediated inflammatory disorder of the central nervous system, characterized by demyelination. Acute disseminated encephalomyelitis predominantly involves the white matter of the brain and spinal cord, and often follows upper respiratory tract infection. We describe a case of acute disseminated encephalomyelitis associated with the influenza A (H1N1) virus. The H1N1 virus usually causes febrile respiratory signs, e.g., fever, cough, and sore throat. Although these signs exhibit a self-limited course, the frequencies of severe complications and death are increasing. To date, only a few reports of acute disseminated encephalomyelitis secondary to the H1N1 virus have been published.

negative: Chest CT findings of COVID-19 pneumonia by duration of symptoms Abstract Purpose To evaluate lung abnormalities on thin-section computed tomographic (CT) scans in patients with COVID-19 and correlate findings to duration of symptoms. Methods In total, 348 CT scans in 112 patients were classified according to the time after the onset of the initial symptoms, namely stage-1 (0–4 days); stage-2 (5–9 days); stage-3 (10–14 days); stage-4 (15–21 days); stage-5 (22–28 days); and stage-6 (＞28 days). Each lung lobe was evaluated for extent affected by ground-glass opacities (GGO), crazy-paving pattern and consolidation, in five categories of percentual severity. Summation of scores from all five lung lobes provided the total CT score (maximal CT score, 25). Results The predominant patterns of lung abnormalities were GGOs, crazy-paving pattern, consolidation and linear opacities. The frequency of crazy-paving pattern, consolidation and linear opacities peaked at stage-3 (62.7 %), stage-4 (75.0 %) and stage-5 (83.1 %), respectively, and decreased thereafter. Total CT scores increased from stage-1 to stage-2 (2.8 ± 3.1, vs. 6.5 ± 4.6, respectively, P < 0.01), and thereafter remained high. The lower lobes were more inclined to be involved with higher CT scores except for stage-1. At stage-6 98.1 % of CT scans still showed abnormalities (CT score 7.5 ± 4.1). Conclusion Thin-section CT could provide semi-quantitative analysis of pulmonary damage severity. This disease changed rapidly at the early stage, then tended to be stable and lasted for a long time.

negative: COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.

negative: Becoming a Faithful Defender: Traditional Chinese Medicine against Coronavirus Disease 2019 (COVID-19). The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.

negative: Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious SARS-CoV-2. The immunopathological characteristics of COVID-19 patients, either systemic or local, have not been thoroughly studied. In the present study, we analyzed both the changes in the cellularity of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells, and NK cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. IL-2, IL-6, and IL-10 were remarkably up-regulated in patients with severe COVID-19. The levels of IL-2 and IL-6 relative to the length of hospital stay underwent a similar "rise-decline" pattern, probably reflecting the therapeutic effect. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-2 and IL-6 are reliable indicators of severe COVID-19.

negative: Study of Non-Pharmacological Interventions on COVID-19 Spread COVID-19 disease has emerged as one of the life threatening threat to the society. It is caused by a novel beta coronavirus. It began as unidentified pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. No vaccine has been produced till now. Mathematical models are used to study impact of different measures used to decrease pandemic. Mathematical models have been designed to estimate the numbers of spreaders in different scenarios in the present manuscript. In the present manuscript, three different mathematical models have been proposed with different scenarios such as screening, quarantine and NPIs for estimating number of virus spreaders. the analysis shows that the numbers of COVID-19 patients will be more without screening the peoples coming from other countries. Since, every people suffering with COVID-19 disease are spreaders. The screening and quarantine with NPIs have been implemented to study their impact on the spreaders. It has been found that NPI measures are able to reduce number of spreaders. The NPI measures reduces the growth of the spread function and providing decision makers more time to prepare with in dealing of the disease.

negative: May patients receiving 5-alpha-reductase inhibitors be in higher risk of COVID-19 complications? COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males.

negative: Machine intelligence design of 2019-nCoV drugs Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.

negative: Gaining Insights into the Codon Usage Patterns of TP53 Gene across Eight Mammalian Species TP53 gene is known as the “guardian of the genome” as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB) is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC(3) and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

negative: Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2 From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.

negative: Characteristics of Endodontic Emergencies during COVID-19 Outbreak in Wuhan Abstract Introduction In late 2019 an outbreak of a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Wuhan, China. A great percentage of patients with this disease developed symptoms of dry cough, malaise and high fever. During this time several patients requiring assessment and treatment of endodontic emergencies were directed to the School and Hospital of Stomatology at Wuhan University (WHUSS). Here, we examined the characteristics of these patients. Methods A total of 96 patients with mean age of 42.24 ± 18.32 years visited General and Emergency Department of WHUSS due to endodontic emergencies during the peak period of February 22 to March 2, 2020. Patient information was collected and organized by date of visit, gender, age, systemic diseases history. Body temperature was measured and acquired for each patient, a coronavirus disease 2019 (COVID-19) epidemiological investigation questionnaire was given to each patient, endodontic diagnosis determined for the offending tooth and verbal numerical rating scale (VNRS) was used to record pain levels. Results Of total patient visits during this period, 50.26% of visits were for endodontic treatment. No patients had fever (>37.2°C). One patient with a confirmed COVID-19 history was admitted after recovery. Three admitted patients had been exposed to confirmed or suspected COVID-19 patients. Twelve admitted patients (12.5%) with mean age of 62.42 ± 13.77 years had a history of systemic diseases. The most common age group for endodontic emergencies was 45-64 years (30.21%) and patients of this group showed significantly higher mean VNRS score compared with that of the 6-19 years group and 20-34 years group (p<0.05). The majority of endodontic emergency diagnosis was diseases of symptomatic irreversible pulpitis (53.10%). Patients who were diagnosed with symptomatic irreversible pulpitis, symptomatic apical periodontitis and acute apical abscess showed significantly higher mean VNRS Score than that of other groups (p<0.05). Conclusion Endodontic emergencies, with symptomatic irreversible pulpitis being the most common, consist of a much higher proportion of dental emergencies in a COVID-19 high risk area than normally. Vital pulp therapy can advantageously reduce treatment time resulting in reduced risk of infection for vital pulp cases. Rubber dam, personal protective equipment and patient screening are of great importance during the COVID-19 outbreak in protecting clinicians.

negative: Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response. The rat coronavirus sialodacryoadenitis virus (SDAV) causes respiratory infection and provides a system for investigating respiratory coronaviruses in a natural host. A viral suspension in the form of a microspray aerosol was delivered by intratracheal instillation into the distal lung of 6-8-week-old Fischer 344 rats. SDAV inoculation produced a 7 % body weight loss over a 5 day period that was followed by recovery over the next 7 days. SDAV caused focal lesions in the lung, which were most severe on day 4 post-inoculation (p.i.). Immunofluorescent staining showed that four cell types supported SDAV virus replication in the lower respiratory tract, namely Clara cells, ciliated cells in the bronchial airway and alveolar type I and type II cells in the lung parenchyma. In bronchial alveolar lavage fluid (BALF) a neutrophil influx increased the population of neutrophils to 45 % compared with 6 % of the cells in control samples on day 2 after mock inoculation. Virus infection induced an increase in surfactant protein SP-D levels in BALF of infected rats on days 4 and 8 p.i. that subsided by day 12. The concentrations of chemokines MCP-1, LIX and CINC-1 in BALF increased on day 4 p.i., but returned to control levels by day 8. Intratracheal instillation of rats with SDAV coronavirus caused an acute, self-limited infection that is a useful model for studying the early events of the innate immune response to respiratory coronavirus infections in lungs of the natural virus host.

negative: Pathological Findings and Management of COVID-19 Patients: A Brief Overview of Modern-day Pandemic Today the world is facing one of the deadliest pandemics caused by COVID-19. This highly transmissible virus has an incubation period of 2 to 14 days. It acts by attaching to the angiotensin-converting enzyme (ACE2) with the help of glycoprotein spikes, which it uses as a receptor. Real-time polymerase chain reaction (PCR; rt-PCR) is the gold standard diagnostic test, and chest X-ray and computed tomography (CT) scan are the other main investigations. Several medications and passive immunization are in use to treat the condition. We searched using PubMed and Google Scholar using keywords such as COVID-19, coronavirus, and their combination with pathological findings, clinical features, management, and treatment to search for relevant published literature. After the removal of duplications and the selection of only published English literature from the past five years, we had a total of 31 papers to review. Most of the COVID-19 affected patients have mild pneumonia symptoms, and those with severe disease have comorbidities. Patients with COVID-19 had pathological findings, like ground-glass opacities, consolidations, pleural effusion, lymphadenopathy, and interstitial infiltration of inflammatory cells. Radiological changes show lung changes such as consolidations and opacities, and the pathological findings were infiltration of inflammatory cells and hyalinization. Patients with mild symptoms should self-quarantine, whereas those with severe acute respiratory distress syndrome (ARDS) are treated in the hospital. Medications under trial include antivirals, antibacterials, antimalarials, and passive immunization. Supportive treatment such as oxygen therapy, extracorporeal membrane oxygenation, and ventilator support can also be used. The symptoms shown by patients are very mild and self-limiting. There is no definitive treatment, although a combination of hydroxychloroquine and azithromycin have shown good results, and passive immunization also shows promising results, their safety profile is yet to be studied in detail.

negative: The effects of COVID-19 pandemic on the provision of urgent surgery: a perspective from the USA Corona virus pandemic has affected all the 50 states in the USA. States such as NY, CA and WA being the most affected. According to the Centers for Disease Control and Prevention (CDC) website, as of 28 March 2020, the total number of cases in the USA is over 103 300 and number of deaths to 1668. In the coming weeks, COVID-19 rates are expected to begin skyrocketing and hit a peak in late April/May/June given lessons learned from China, Italy and others. COVID-19 has been declared a pandemic by the World Health Organization (WHO) as confirmed cases approach 575 444 patients with 26 654 deaths across over 160 countries, as of 28 March 2020. There is a lot of impact on management of the urgent and emergent cases. This article highlights the changes that are being made in delivering urgent and emergent surgical care during the pandemic.

negative: Influenza A H1N1 2009 (Swine Flu) and Pregnancy The Influenza A H1N1 pandemic (A H1N1) occurred between June 2009 and August 2010. Although the pandemic is now over, the virus has emerged as the predominant strain in the current seasonal influenza phase in the northern hemisphere. The A H1N1 influenza is a novel strain of the influenza A virus and is widely known as swine flu. The virus contains a mixture of genetic material from human, pig and bird flu virus. It is a new variety of flu which people have not had much immunity to. Much has been learnt from the Pandemic of 2009/2010 but the messages about vaccination and treatment seem to be taken slowly by the clinical profession. Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery. The median duration of illness is around seven days. This influenza typically affects the younger age group i.e. from the ages of 5–65 years. Current experience shows that the age group experiencing increased morbidity and mortality rates are in those under 65 years of age. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. In the United Kingdom, twelve maternal deaths were reported to be associated with the H1N1 virus during the pandemic and clear avoidable factors were identified (Modder, Review of Maternal Deaths in the UK related to A H1N1 2009 influenza (CMACE). www.cmace.org.uk, 2010). The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate (Yates et al. Health Technol Assess 14(34):109–182, 2010). There continues to be a low uptake of the flu vaccine and commencement of antiviral treatment for pregnant women.

negative: Long-term intubation and high rate of tracheostomy in COVID-19 patients might determine an unprecedented increase of airway stenoses: a call to action from the European Laryngological Society INTRODUCTION: The novel Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, may need intensive care unit (ICU) admission in up to 12% of all positive cases for massive interstitial pneumonia, with possible long-term endotracheal intubation for mechanical ventilation and subsequent tracheostomy. The most common airway-related complications of such ICU maneuvers are laryngotracheal granulomas, webs, stenosis, malacia and, less commonly, tracheal necrosis with tracheo-esophageal or tracheo-arterial fistulae. MATERIALS AND METHODS: This paper gathers the opinions of experts of the Laryngotracheal Stenosis Committee of the European Laryngological Society, with the aim of alerting the medical community about the possible rise in number of COVID-19-related laryngotracheal stenosis (LTS), and the aspiration of paving the way to a more rationale concentration of these cases within referral specialist airway centers. RESULTS: A range of prevention strategies, diagnostic work-up, and therapeutic approaches are reported and framed within the COVID-19 pandemic context. CONCLUSIONS: One of the most important roles of otolaryngologists when encountering airway-related signs and symptoms in patients with previous ICU hospitalization for COVID-19 is to maintain a high level of suspicion for LTS development, and share it with colleagues and other health care professionals. Such a condition requires specific expertise and should be comprehensively managed in tertiary referral centers.

negative: Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.

negative: Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency Abstract According to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland, more than two and half million cases of coronavirus disease 2019 (COVID-19), caused by a newly discovered virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed on April 20, 2020 (Nature, 2020b). Since the emergence of this infectious disease in Asia (Wuhan, China) late last year, it has been subsequently span to every continent of the world except Antarctica (Rodríguez-Morales et al., 2020). Along with a foothold in every country, the current disease pandemic is disrupting practically every aspect of life all over the world. As the outbreak are continuing to evolve, several research activities have been conducted for better understanding the origin, functions, treatments, and preventions of this novel coronavirus. This review will be a summa of the key features of novel coronavirus (nCoV), the virus causing disease 2019 and the present epidemic situation worldwide up to April 20, 2020. It is expected that this record will play an important role to take more preventive measures for overcoming the challenges faced during this current pandemic.

negative: Non-steroidal anti-inflammatory drugs and covid-19.

negative: Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. Observations: This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as stroke, impairment of consciousness, seizure, and encephalopathy, have also been reported. Conclusions and Relevance: Recognition and understanding of the range of neurological disorders associated with COVID-19 may lead to improved clinical outcomes and better treatment algorithms. Further neuropathological studies will be crucial to understanding the pathogenesis of the disease in the central nervous system, and longitudinal neurologic and cognitive assessment of individuals after recovery from COVID-19 will be crucial to understand the natural history of COVID-19 in the central nervous system and monitor for any long-term neurologic sequelae.

negative: Planning horizon affects prophylactic decision-making and epidemic dynamics The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon—the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals’ payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual’s perceived risk of infection.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Emergence, History, Basic and Clinical Aspects Abstract In late December 2019, the world woke to a reality of a pandemic of Coronavirus Disease (COVID-19), elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which belongs to a group of β-coronavirus. The potential to cause life-threatening respiratory failure and rapid transmission puts COVID-19 in the list of Public Health Emergency of International Concern (PHEIC). In the last two decades, this is the 3rd deadliest Coronavirus pandemic, following SARS which lasted between 2002 and 2003 and Middle East Respiratory Syndrome (MERS) from 2012 till date. Globally and as of April 1st 2020, COVID-19 has affected 924,688 individuals in over 200 countries, causing 46,368 fatalities. While the SARS-CoV-2 originated in China with over 82,724 confirmed cases and more than 3000 deaths as at the time of writing this review, the rapid transmission of SARS-CoV-2 has resulted in exponential increase in the number of cases outside of China to about 10 times the report case and death in mainland China. SARS-CoV-2 is suspected to be zoonotic in nature as genetic studies have shown sequence similarity to viruses originating from bats. Extreme precautionary measures, such as curfew, shutting of borders and quarantining of individuals suspected to be infected have been instituted with immediate effect; however, due to individuals that are asymptomatic, uncontrolled human-to-human transmission has resulted in exponential infection rate and numerous loss of lives even with this lockdown measures. This review article summarizes the developing situation surrounding the SARS-CoV-2 pandemic with respect to its epidemiology, unique genomic structure, possible origins, transmission, pathogenesis, comparison with other deadly species of Coronaviruses (CoV) and emerging treatment strategies built on informed literature.

negative: Understanding epidemic data and statistics: A case study of COVID‐19 The 2019 novel‐coronavirus (COVID‐19) has affected 181 countries with approximately 1197405 confirmed cases (by 5th April). Understanding the transmission dynamics of the infection in each country which got affected on a daily basis and evaluating the effectiveness of control policies are critical for our further actions. To date, the statistics of COVID‐19 reported cases show that more than 80% of infected are mild cases of disease, around 14% of infected have severe complications, and about 5% are categorized as critical disease victims. Today's report (5th April 2020; daily updates in the prepared website) shows that the confirmed cases of COVID‐19 in the United States, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092, respectively. Calculating the total case fatality rate (CFR) of Italy (4th April 2020), about 13.3% of confirmed cases have passed away. Compared with South Korea's rate of 1.8% (seven times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. Some effective policies that yielded significant changes in the trend of cases were the lockdown policy in China, Italy, and Spain (the effect observed after some days), the shutdown of all nonessential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.

negative: COVID-19 and the elderly: insights into pathogenesis and clinical decision-making The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

negative: Lessons Learned from 9/11: Mental Health Perspectives on the COVID-19 Pandemic Abstract The COVID-19 pandemic will likely lead to high rates of PTSD, depression, and substance misuse among survivors, victims’ families, medical workers, and other essential personnel. The mental health response to the 9/11/01 terrorist attacks, culminating in a federally-funded health program, provides a template for how providers may serve affected individuals. Drawing on the 9/11 experience, we highlight effective prevention measures, likely short and long-term treatment needs, vulnerable subgroups, and important points of divergence between 9/11 and the COVID-19 pandemic. Mental health monitoring, early identification of at-risk individuals, and treatment irrespective of financial barriers is essential for minimizing chronic distress.

negative: Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China Background: Severe patients with 2019 novel coronavirus (2019-nCoV) pneumonia progressed rapidly to acute respiratory failure. We aimed to evaluate the definite efficacy and safety of corticosteroid in the treatment of severe COVID-19 pneumonia. Methods: Forty-six hospitalized patients with severe COVID-19 pneumonia hospitalized at Wuhan Union Hospital from January 20 to February 25, 2020, were retrospectively reviewed. The patients were divided into two groups based on whether they received corticosteroid treatment. The clinical symptoms and chest computed tomography(CT) results were compared. Results: A total of 26 patients received intravenous administration of methylprednisolone with a dosage of 1-2mg/kg/d for 5-7 days, while the remaining patients not. There was no significant difference in age, sex, comorbidities, clinical or laboratory parameters between the two groups on admission. The average number of days for body temperature back to the normal range was significantly shorter in patients with administration of methylprednisolone when compared to those without administration of methylprednisolone (2.06 ± 0.28 vs. 5.29 ± 0.70, P=0.010). The patients with administration of methylprednisolone had a faster improvement of SpO2, while patients without administration of methylprednisolone had a significantly longer interval of using supplemental oxygen therapy (8.2days[IQR 7.0-10.3] vs. 13.5days(IQR 10.3-16); P<0.001). In terms of chest CT, the absorption degree of the focus was significantly better in patients with administration of methylprednisolone. Conclusion: Our data indicate that in patients with severe COVID-19 pneumonia, early, low-dose and short-term application of corticosteroid was associated with a faster improvement of clinical symptoms and absorption of lung focus.

negative: Dysphagia in COVID‐19 –multilevel damage to the swallowing network? We read with great interest the article “COVID‐19: what if the brain had a role in causing the deaths?” by Tassorelli and co‐workers, in which the authors generate and summarize hypotheses how SARS‐CoV‐2 may enter the peripheral and central nervous system and cause life‐threatening complications [1]. With this letter we would like to contribute to this discussion by highlighting how different complications of COVID‐19 may result in damage to central and peripheral parts of the swallowing network leading to dysphagia in critically ill COVID‐survivors.

negative: Is there hope for the Hajj? Using the SIR Model to Forecast COVID-19 Progression in the City of Makkah Abstract: Background: The Hajj is the largest annual gathering in the world, and it is a very important event for every Muslim. Makkah annually receives three million pilgrims who perform Hajj. Although precautionary measures have been taken in Saudi Arabia to slow down the spread of COVID-19, such as locking down the most affected cities, practicing social distancing, and applying the infection-control precautions, the number of cases has increased. The total confirmed number of cases in Makkah was 10,709 with 127 deaths as of May 16, 2020. Aims of the study: Forecasting the COVID-19 progression in the city of Makkah will help the policymakers decide if the Hajj will be able to operate this year. Thus, to see a clear picture of the fight against COVID-19 for the economy and healthcare industry in Saudi Arabia, specifically in Makkah, the SIR model will predict COVID-19 progression in the city of Makkah. Method: The Susceptible, Infected, and Recovered (SIR) model has been used to track the transmission dynamics and growth among the city of Makkah. The growth index was calculated, according to the data from March 16 until May 9. The estimated vital epidemiological parameters, such as forecasting works and transmission rates, were done. Result: The data showed an interesting result about the peak of the disease progression. It is projected to occur around the 12th day after running the model. According to the model, the peak time will be around the 22nd of May. Then, the number of cases will start to decrease. Conclusion: Using the SIR model, the result predicts the disease progression peak and an estimated end of COVID-19 in the city of Makkah to help the policymakers decide if the Hajj will be able to operate this year.

negative: The role of CT in case ascertainment and management of COVID-19 pneumonia in the UK: insights from high-incidence regions

negative: Towards treatment planning of COVID-19: Rationale and hypothesis for the use of multiple immunosuppressive agents: anti-antibodies, immunoglobulins, and corticosteroids Abstract The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.

negative: Statistical Issues and Recommendations for Clinical Trials Conducted During the COVID-19 Pandemic The COVID-19 pandemic has had and continues to have major impacts on planned and ongoing clinical trials. Its effects on trial data create multiple potential statistical issues. The scale of impact is unprecedented, but when viewed individually, many of the issues are well defined and feasible to address. A number of strategies and recommendations are put forward to assess and address issues related to estimands, missing data, validity and modifications of statistical analysis methods, need for additional analyses, ability to meet objectives and overall trial interpretability.

negative: Risks Posed to Corneal Transplant Recipients by COVID-19-Affected Donors. The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant human disease, COVID-19, will likely have a significant impact on the corneal tissue donor pool. Current recommendations from the United States and global eye bank associations call for the outright avoidance of tissues from donors recently infected with or exposed to COVID-19. This conservative recommendation is currently appropriate given the reported ocular sequelae, tear film viral detectability, and transmissibility of COVID-19. However, the rapidly increasing global prevalence and mortality of COVID-19 threatens the tenability of current tissue exclusion guidelines, and may necessitate their relaxation in the near future.

negative: Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia BACKGROUND: Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI. METHODS: In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes. RESULTS: We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI. CONCLUSIONS: Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.

negative: The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19 Abstract The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated. Moreover, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization. This provided rationale for the use of anti-rheumatic drugs as potential treatments for this severe viral infection. Other agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. The anti-viral aspect of immunosuppressants towards a variety of viruses has been known since long time and it is herein discussed in the view of searching for a potential treatment for SARS-CoV-2 infection.

negative: Public Health Aspects of COVID-19 Infection with Focus on Cardiovascular Diseases INTRODUCTION: COVID-19 is the disease caused by an infection of the SARS-CoV-2 virus, first identified in the city of Wuhan, in China’s Hubei province in December 2019. COVID-19 was previously known as 2019 Novel Coronavirus (2019-nCoV) respiratory disease before the World Health Organization (WHO) declared the official name as COVID-19 in February 2020. AIM: The aim of this study is to search scientific literature in the biomedicine and analyzed current results of investigations regarding morbidity and mortality rates as consequences of COVID-19 infection of Cardiovascular diseases (CVD), and other most common chronic diseases which are on the top mortality and morbidity rates in almost all countries in the world. Also, to propose most useful measures how to prevent patients to keep themselves against COVID-19 infection. METHODS: We used method of descriptive analysis of the published papers with described studies about Corona virus connected with CVD, and, also, Guidelines proposed by World Health Organization (WHO) and European Society of Cardiology (ESC), and some other international associations which are included in global fighting against COVID-19 infection. RESULTS: After searching current scientific literature we have acknowledged that not any Evidence Based Medicine (EBM) study in the world during last 5 months from the time when first cases of COVID-10 infection was detected. Also, there is no unique proposed ways of treatments and drugs to protect patients, especially people over 65 years old, who are very risk group to be affected with COVID-19. Expectations that vaccine against COVID-19 will be produced optimal during at least 10 months to 2 years, and in all current Guidelines most important proposed preventive measures are the same like which one described in Strategic documents of WHO, in statements of Declaration of Primary Health Care in Alma Ata in 1978. CONCLUSION: WHO proposed preventive measures can be helpful to everybody. Physicians who work at every level of Health Care Systems, but especially at primary health care level, must follow those recommendations and teach their patients about it. But, the fact is that current focus of COVID-19 epidemic has targeted on protection of physical health of population in global, however, the influence on mental health which will be one of the important consequences of COVID-19 pandemic in the future, and which could be declared as «Post-coronavirus Stress Syndrome„ (PCSS) could be bigger challenge for Global Public Health.

negative: The impact of coronavirus infectious disease 19 (COVID-19) on oral health Health services across the world face an unprecedented situation as a result of a global COVID-19 outbreak. Urgent joined research efforts regarding the SARS-COV-2 rapid tests, accurate diagnosis, especially early recognition, and effective treatment of life-threatening complications would be highly desirable for humanity and medical workforce all over the world that try to combat a current global pandemic threat. Due to indirect complex effect, intensified COVID-19 therapies and multi-drug treatment, it is believed that some oral conditions could be aggravated by COVID-19 disease, particularly those with autoimmune aetiology, linked to compromised immune system or long-term pharmacotherapy.

negative: Measuring COVID-19 and Influenza in the Real World via Person-Generated Health Data Background: Since the beginning of the COVID-19 pandemic data from smartphones and connected sensors has been used to learn about symptoms presentation and management outside the clinic walls. However, reports on the validity of such data are still sparse, especially when it comes to symptom progression and relevance of wearable sensors. Objective: To understand the relevance of Person-GeneratedHealth Data (PGHD) as a means for early detection, monitoring and management of COVID-19 in everyday life. This includes quantifying prevalence and progression of symptoms from self-reports as well as changes in activity and physiological parameters continuously measured from wearable sensors, and contextualizing findings for COVID-19 patients with those from cohorts of flu patients. Design, Setting, and Participants: Retrospective digital cohort study of individuals with a self-reported positive SARS-CoV-2 or influenza test followed over the period 2019-12-02 to2020-04-27. Three cohorts were derived: Patients who self-reported being diagnosed with flu prior to the SARS-CoV-2 pandemic (N=6270, of which 1226 also contributed sensorPGHD); Patients who reported being diagnosed with flu during the SARS-CoV-2 pandemic (N=426, of which 85 also shared sensor PGHD); and patients who reported being diagnosed withCOVID-19 (N=230, of which sensor PGHD was available for 41).The cohorts were derived from a large-scale digital participatory surveillance study designed to track Influenza-like Illness(ILI) incidence and burden over time. Exposures: Self-reported demographic data, comorbidities, and symptoms experienced during a diagnosed ILI episode, including SARS-CoV-2.Physiological and behavioral parameters measured daily from commercial wearable sensors, includingResting Heart Rate (RHR), total step count, and nightly sleep hours. Main Outcomes and Measures: We investigated the percent-age of individuals experiencing symptoms of a given type (e.g.shortness of breath) across demographic groups and over time. We examined illness duration, and care seeking behavior, and how RHR, step count, and nightly sleep hours deviated from expected behavior on healthy days over the course of the infection episode. Results: Self-reported symptoms of COVID-19 present differently from flu. COVID-19 cases tended to last longer than flu(median of 12 vs. 9 days), are uniquely characterized by chest pain/pressure, shortness of breath, and anosmia. The fraction of elevated RHR measurements collected daily from commercial wearable devices rise significantly in the 2 days surrounding ILI symptoms onset, but does not appear to do so in a way specific to COVID-19. Steps lost due to COVID-19 persists for longer. Conclusion and Relevance: PGHD can be a valid source of longitudinal real world data to detect and monitor COVID-19-related symptoms and behaviors at population scale. PGHD may provide continuous, near realtime feedback to intervention effectiveness that otherwise requires waiting for symptoms to develop into contacts with the healthcare system. It has also the potential to increase pre-test probability of other downstream diagnostics. To effectively leverage PGHD for participatory surveillance it is crucial to invest in the creation of trusted, long-term communication channels with individuals through whichdata can be efficiently collected, consented, and contextualized,while protecting the privacy of individuals and ultimately facilitating the transition in and out of care.

negative: SARS-CoV-2 pandemic expanding in sub-Saharan Africa: Considerations for COVID-19 in people living with HIV

negative: Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study The aim of this study was to develop an appropriate anti-viral drug against the SARS-CoV-2 virus. An immediately qualifying strategy would be to use existing powerful drugs from various virus treatments. The strategy in virtual screening of antiviral databases for possible therapeutic effect would be to identify promising drug molecules, as there is currently no vaccine or treatment approved against COVID-19. Targeting the main protease (pdb id: 6LU7) is gaining importance in anti-CoV drug design. In this conceptual context, an attempt has been made to suggest an in silico computational relationship between US-FDA approved drugs, plant-derived natural drugs, and Coronavirus main protease (6LU7) protein. The evaluation of results was made based on Glide (Schrödinger) dock score. Out of 62 screened compounds, the best docking scores with the targets were found for compounds: lopinavir, amodiaquine, and theaflavin digallate (TFDG). Molecular dynamic (MD) simulation study was also performed for 20 ns to confirm the stability behaviour of the main protease and inhibitor complexes. The MD simulation study validated the stability of three compounds in the protein binding pocket as potent binders.

negative: Complications of Orbital Emphysema in a COVID-19 Patient

negative: Facing the COVID‐19 outbreak: What should we know and what could we do? A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.

negative: Treatable traits and therapeutic targets: Goals for systems biology in infectious disease Abstract Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing. A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be static – serial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients.

negative: Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.

negative: COMMENTARY: COMPLICATIONS RESCUE AND LONG-TERM SURVIVAL - WHERE DO THE PILLARS OF HERCULES LIE?

negative: CoViD-19 and stress in the pandemic: "sanity is not statistical" CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including . The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.

negative: Outbreak of Porcine Epidemic Diarrhea in Suckling Piglets, China

negative: Lessons from lesions: the effects of olfactory bulbectomy Olfactory bulb removal has been used to examine a wide-ranging number of topics. The present review outlines the categories of studies employing the technique, discusses some problems with the methodology and with previous interpretations of observed results, and suggests some potential avenues of investigation.

negative: A classifier prediction model to predict the status of Coronavirus COVID-19 patients in South Korea OBJECTIVE: Coronavirus COVID-19 further transmitted to several countries globally. The status of the infected cases can be determined basing on the treatment process along with several other factors. This research aims to build a classifier prediction model to predict the status of recovered and death coronavirus CovID-19 patients in South Korea. MATERIALS AND METHODS: Artificial neural network principle is used to classify the collected data between February 20, 2020 and March 9, 2020. The proposed classifier used different seven variables, namely, country, infection reason, sex, group, confirmation date, birth year, and region. The most effective variables on recovered and fatal cases are analyzed based on the neural network model. RESULTS: The results found that the proposed predictive classifier efficiently predicted recovered and death cases. Besides, it is found that discovering the infection reason would increase the probability to recover the patient. This indicates that the virus might be controllable based on infection reasons. In addition, the earlier discovery of the disease affords better control and a higher probability of being recovered. CONCLUSIONS: Our recommendation is to use this model to predict the status of the patients globally.

negative: The globe on the spotlight: Coronavirus disease 2019 (Covid-19)

negative: CT imaging changes of corona virus disease 2019(COVID-19): a multi-center study in Southwest China BACKGROUND: Since the first case of a coronavirus disease 2019 (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Southwest China. The aim of this study was to describe the imaging manifestations of hospitalized patients with confirmed COVID-19 infection in southwest China. METHODS: In this retrospective study, data were collected from 131 patients with confirmed coronavirus disease 2019 (COVID-19) from 3 Chinese hospitals. Their common clinical manifestations, as well as characteristics and evolvement features of chest CT images, were analyzed. RESULTS: A total of 100 (76%) patients had a history of close contact with people living in Wuhan, Hubei. The clinical manifestations of COVID-19 included cough, fever. Most of the lesions identified in chest CT images were multiple lesions of bilateral lungs, lesions were more localized in the peripheral lung, 109 (83%) patients had more than two lobes involved, 20 (15%) patients presented with patchy ground glass opacities, patchy ground glass opacities and consolidation of lesions co-existing in 61 (47%) cases. Complications such as pleural thickening, hydrothorax, pericardial effusion, and enlarged mediastinal lymph nodes were detected but only in rare cases. For the follow-up chest CT examinations (91 cases), We found 66 (73%) cases changed very quickly, with an average of 3.5 days, 25 cases (27%) presented absorbed lesions, progression was observed in 41 cases (46%), 25 (27%) cases showed no significant changes. CONCLUSION: Chest CT plays an important role in diagnosing COVID-19. The imaging pattern of multifocal peripheral ground glass or mixed consolidation is highly suspicious of COVID-19, that can quickly change over a short period of time.

negative: Actualités sur le syndrome respiratoire aigu sévère Résumé Propos et points forts. – Le syndrome respiratoire aigu sévère (SRAS) a récemment été reconnu comme étant associé à une infection virale émergente, hautement contagieuse et pouvant être mortelle. Actualités. – À fin juin 2003, plus de 8500 cas d’infections humaines et 800 décès ont été rapportés dans 30 pays. L’agent responsable de cette infection a été identifié comme étant un nouveau coronavirus. La présentation clinique, les anomalies biologiques et radiologiques, ainsi que l’évolution et le traitement des patients infectés par ce virus sont décrits dans cet article. Perspectives et projets. – La recherche de thérapeutiques efficaces et de vaccins est en cours d’évaluation. Abstract Introduction. – The severe acute respiratory syndrome (SARS) has recently been recognised as a new clinical entity and a new emerging infectious disease that is highly contagious with significant mortality. Current knowledge and key points. – By the end of 17 June 2003, a total of 8500 cases included 800 deaths had been reported from 30 countries. The cause of SARS has been identified as a new corona virus. In this manuscript, we describe the clinical features, biological findings, virological tests, radiological assessment, outcome and treatments of this infection. Future. – Research on specific therapies and vaccines is on-going.

negative: Exposure to air pollution and COVID-19 mortality in the United States: A nationwide cross-sectional study Objectives: United States government scientists estimate that COVID-19 may kill tens of thousands of Americans. Many of the pre-existing conditions that increase the risk of death in those with COVID-19 are the same diseases that are affected by long-term exposure to air pollution. We investigated whether long-term average exposure to fine particulate matter (PM2.5) is associated with an increased risk of COVID-19 death in the United States. Design: A nationwide, cross-sectional study using county-level data. Data sources: COVID-19 death counts were collected for more than 3,000 counties in the United States (representing 98% of the population) up to April 22, 2020 from Johns Hopkins University, Center for Systems Science and Engineering Coronavirus Resource Center. Main outcome measures: We fit negative binomial mixed models using county-level COVID-19 deaths as the outcome and county-level long-term average of PM2.5 as the exposure. In the main analysis, we adjusted by 20 potential confounding factors including population size, age distribution, population density, time since the beginning of the outbreak, time since state issuance of the stay-at-home order, hospital beds, number of individuals tested, weather, and socioeconomic and behavioral variables such as obesity and smoking. We included a random intercept by state to account for potential correlation in counties within the same state. We conducted more than 68 additional sensitivity analyses. Results: We found that an increase of only 1 μg/m3 in PM2.5 is associated with an 8% increase in the COVID-19 death rate (95% confidence interval [CI]: 2%, 15%). The results were statistically significant and robust to secondary and sensitivity analyses. Conclusions: A small increase in long-term exposure to PM2.5 leads to a large increase in the COVID-19 death rate. Despite the inherent limitations of the ecological study design, our results underscore the importance of continuing to enforce existing air pollution regulations to protect human health both during and after the COVID-19 crisis. The data and code are publicly available so our analyses can be updated routinely.

negative: Why all COVID-19 Hospitals should have Mental Health Professionals: The importance of mental health in a worldwide crisis! Abstract COVID-19 pandemic has led to a worldwide crisis. At present, everyone is focusing on the prevention of COVID-19 infection, preparing and discussing issues related to physical health consequences. However, it is important to understand that the life-threatening negative physical health consequences are going to be faced by a few, but everyone is going to face the negative mental health consequences of the pandemic. At various places COVID-19 hospitals are being established, to address the physical health consequences of the pandemic. However, mental health professionals have not been very actively involved in the management of people going through this pandemic. This viewpoint discusses the mental health consequences of the pandemic for the health care workers, people who are undergoing quarantine, people who are admitted to the COVID-19 hospitals, and those who have recovered from the infection. The article also highlights the mental health needs of people at different levels and the kind of interventions, which may be carried out.

negative: Redeploying plant defences Epidemic diseases are not a new phenomenon, but easy access to transport in the modern world has accelerated their spread. Perhaps some botanical understanding can help slow them down.

negative: Démarche diagnostique et thérapeutique devant une suspicion d'infection bronchique et pulmonaire aiguë chez l'immunocompétent Résumé Les infections respiratoires regroupent trois entités dont les indications thérapeutiques sont différentes et qu'il importe de reconnaître : les bronchites aiguës, les pneumopathies aiguës et les exacerbations de bronchite chronique. Les bronchites aiguës sont très fréquentes, de diagnostic facile et d'évolution bénigne. Leur étiologie est en règle virale. Elles ne justifient pas d'antibiothérapie. Les pneumopathies aiguës sont, à l'inverse, peu fréquentes, mais présentent un risque évolutif potentiellement grave et restent la sixième cause de mortalité. Leur étiologie est le plus souvent bactérienne chez l'adulte et elles requièrent toujours une antibiothérapie. Leur diagnostic clinique repose sur des signes de présomption : fièvre, tachycardie, tachypnée, douleur thoracique, râles crépitants en foyer et impression de gravité. Elles justifient la réalisation d'une radiographie pulmonaire. Les exacerbations de bronchite chronique peuvent être d'origine bactérienne, virale ou non infectieuse. Les indications de l'antibiothérapie dépendent de la probabilité de l'origine bactérienne (augmentation du volume et de la purulence de l'expectoration, apparition ou aggravation d'une dyspnée) et du stade de la bronchopathie chronique (simple, obstructive sans insuffisance respiratoire chronique, insuffisance respiratoire chronique). Abstract Respiratory infections include acute bronchitis, acute pneumonia and acute exacerbation of chronic bronchitis. Each of these diseases has its own therapeutic approach, making important a good differential diagnosis. Acute bronchitis are very frequent, easy to diagnose and have a benign evolution. The etiology is usually viral. The treatment doesn’t require antibiotics. Conversely, acute pneumonia is infrequent but has to be considered as a serious illness; it remains the sixth cause of death. In adults, pneumonia is usually due to bacteria and antibiotherapy is always required. Clinical diagnosis is based on presumption signs: fever, tachycardia, tachypnea, thoracic pain, localized rales and an overall feeling of severity. A chest X-ray is required. Acute exacerbation of chronic bronchitis can be due to bacteria, virus or a non infectious cause. Antibiotherapy indications are based on the probability of bacterial etiology (increased volume and purulence of sputum, apparition or increase of dyspnea) and on the severity of the chronic bronchitis (chronic bronchitis, chronic obstructive pulmonary disease without respiratory insufficiency or chronic respiratory insufficiency).

negative: Mortality from COVID-19 in 12 countries and 6 states of the United States Importance: Reliable estimates of COVID-19 mortality are crucial to aid control strategies and to assess the effectiveness of interventions. Objective: Project COVID-19 mortality trends to October 1, 2020, in 12 countries or regions that constitute >90% of the global COVID-19 deaths reported as of April 12, 2020. Design, Setting, and Participants: The Global COVID-19 Assessment of Mortality (GCAM) is an open, transparent, and continuously updated (www.cghr.org/covid) statistical model that combines actual COVID-19 mortality counts with Bayesian inference to forecast COVID-19 deaths, the date of peak deaths, and the duration of excess mortality. The analyses covered a total of 700 million population above age 20 in 12 countries or regions: USA; Italy; Spain; France; UK; Iran; Belgium; a province of China (Hubei, which accounted for 90% of reported Chinese deaths); Germany; the Netherlands; Switzerland; and Canada; and six US states: New York, New Jersey, Michigan, Louisiana, California, and Washington. Results: Forecasted deaths across the 12 current high-burden countries sum 167,000 to 593,000 (median 253,000). The trajectory of US deaths (49,000-249,000 deaths; median 86,000)- over half of which are expected in states beyond the initial six states analysed in this study- will have the greatest impact on the eventual total. Mortality ranges are 25,000-109,000 (median 46,000) in the UK; 23,000-31,000 (median 26,000) in Italy; 21,000-37,000 (median 26,000) in France and 21,000-32,000 (median 25,000) in Spain. Estimates are most precise for Hubei, China, where the epidemic curve is complete, and least precise in California, where it is ongoing. New York has the highest cumulative median mortality rate per million (1135), about 12-fold that of Germany. Mortality trajectories are notably flatter in Germany, California, and Washington State, each of which took physical distancing and testing strategies seriously. Using past country-specific mortality as a guide, GCAM predicts surge capacity needs, reaching more than twice existing capacity in a number of places., In every setting, the results might be sensitive to undercounts of COVID-19 deaths, which are already apparent. Conclusion and Relevance: Mortality from COVID-19 will be substantial across many settings, even in the best case scenario. GCAM will provide continually updated and increasingly precise estimates as the pandemic progresses.

negative: Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID‐19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.

negative: Understanding of COVID‐19 based on current evidence Since December 2019, a series of unexplained pneumonia cases have been reported in Wuhan, China. On 12 January 2020, the World Health Organization (WHO) temporarily named this new virus as the 2019 novel coronavirus (2019‐nCoV). On 11 February 2020, the WHO officially named the disease caused by the 2019‐nCoV as coronavirus disease (COVID‐19). The COVID‐19 epidemic is spreading all over the world, especially in China. Based on the published evidence, we systematically discuss the characteristics of COVID‐19 in the hope of providing a reference for future studies and help for the prevention and control of the COVID‐19 epidemic.

negative: Estimation of SARS-CoV-2 emissions from non-symptomatic cases Importance: Cases of the coronavirus disease 2019 (COVID-19) with no or mild symptoms were reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome virus (SARS-COV-2) was found at very high concentrations in swab and sputum of such cases. Objective: We aimed to estimate virus release from such cases into different aerosol sizes by normal breathing and coughing, and what exposure can result from this in a room shared with such as case. Data Sources and Model: We combined the size-distribution of exhaled breath aerosols for coughing and normal breathing with viral sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50m3, the size of a small office or medical exam room. Results: The estimated viral load in aerosols emitted by patients while breathing normally was on average 0.34 copies/cm3 and could go up to 11.5 copies/cm3. The corresponding numbers for coughing patients were 10,900 copies/cm3 and 366,000 copies/cm3, respectively, per cough. The resulting concentrations in a room with a coughing emitter were always very high, up to 2.02*10^9 copies/m3. However, also regular breathing aerosol from high emitters was predicted to lead to several thousand copies/m3. Conclusions and Relevance: These very high predicted virus concentrations may provide an explanation why for COVID-19, frequent community transmissions from non-symptomatic cases and also high infection rates in medical staff in hospital settings were reported. Our findings suggest that strict respiratory protection is needed when there is a chance to be in the same room with a patient - whether symptomatic or not - especially if this was for a prolonged time.

negative: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus. After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.

negative: Pandemic Recovery Using a Covid-Minimal Cancer Surgery Pathway Abstract The Covid-19 pandemic has created unprecedented disruption in health care delivery around the world. In an effort to prevent hospital-acquired Covid-19 infections, most hospitals have severely curtailed elective surgery, performing only surgeries if the patient’s survival or permanent function would be compromised by a delay in surgery. As hospitals emerge from the pandemic, it will be necessary to progressively increase surgical activity at a time when hospitals continue to care for Covid-19 patients. In an attempt to mitigate the risk of nosocomial infection, we have created a patient care pathway designed to minimize risk of exposure of patients coming in to the hospital for scheduled procedures. The “Covid-minimal surgery pathway” is a predetermined patient flow, that dictates the locations, personnel and materials that come in contact with our cancer surgery population, designed to minimize risk for virus transmission. We outline the approach that allowed a large academic medical center to create a Covid-minimal cancer surgery pathway within 7 days of initiating discussions. Although the pathway represents a combination of recommended practices, there is not data to support its efficacy. We share the pathway concept and our experience so that others wishing to similarly align staff and resources towards the protection of patients, may have an easier time navigating the process.

negative: Efficacy of chloroquine versus lopinavir/ritonavir in mild/general COVID-19 infection: a prospective, open-label, multicenter, randomized controlled clinical study BACKGROUND: The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment has yet been confirmed. The adage “old drug, new trick” in this context may suggest the important therapeutic potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals. Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir. METHODS/DESIGN: This is a prospective, open-label, randomized controlled, multicenter clinical study. The study consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-sided tests with a statistical significance level of 5%. DISCUSSION: This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity and is safe, it could be tested as a future COVID-19 treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR2000029741. Registered on 11 February 2020.

negative: Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. What are the implications for the commencement of elective surgery?

negative: Acute gastrointestinal injury in critically ill patients with coronavirus disease 2019 in Wuhan, China Background: To investigate the prevalence and outcomes of acute gastrointestinal injury (AGI) in critically ill patients with coronavirus disease 2019 (COVID-19). Methods: In this clinical retrospective study, demographic data, laboratory parameters, AGI grades, clinical severity and outcomes were collected. The primary endpoints were AGI incidence and 28-day mortality, the secondary endpoints were organ dysfunction and septic shock incidence. Results: From February 10 to March 10 2020, 83 critically ill patients of 1314 patients with COVID-19 were enrolled. Seventy-two (86.7%) patients had AGI during hospital stay, of them, 30 had AGI grade I, 35 had AGI grade II, 5 had AGI grade III, and 2 had AGI grade IV. The incidence of AGI grade II and above was 50.6%. As of March 16, 40 (48.2%) patients died within 28 days of admission, the median hospital stay was 12.0 days, ranging from 3 days to 27 days. Multiple organ dysfunction syndrome developed in 58 (69.9%) patients, septic shock in 16 (19.3%) patients. Patients with worse AGI grades had worse clinical variables, higher septic shock incidence and 28-day mortality. Sequential organ failure assessment scores (SOFA) (95% CI, 1.374-2.860; P <0.001), white blood cell (WBC) counts (95% CI, 1.037-1.379; P =0.014), duration of mechanical ventilation (MV) (95% CI, 1.020-1.340; P =0.025) were risk factors for the development of AGI grade II and above. Non-survivors were accompanied by higher incidence of AGI grade III to IV than survivors (17.5% vs. 0.0%, P =0.004). Conclusions: The AGI incidence was 86.7%, and hospital mortality was 48.2% in critically ill patients with COVID-19. SOFA scores, WBC counts, and duration of MV were risk factors for the development of AGI grade II and above. Patients with worse AGI grades had worse clinical severity variables, higher septic shock incidence and 28-day mortality.

negative: Sex differences in clinical findings among patients with coronavirus disease 2019 (COVID-19) and severe condition Objective: To compare the sex differences in the clinical findings among patients with severe coronavirus disease 2019 (COVID-19). Methods: We retrospectively collected data of 47 patients diagnosed as severe type of COVID-19 from February 8 to 22, 2020, including demographics, illness history, physical examination, laboratory test, management, and compared differences between men and women. Results: Of the 47 patients, 28 (59.6%) were men. The median age was 62 years, and 30 (63.8%) had comorbidities. The initial symptoms were mainly fever (34 [72.3%]), cough (36 [76.6%]), myalgia (5 [10.6%]) and fatigue (7 [14.9%]). Procalcitonin level was higher in men than in women (0.08 vs. 0.04ng/ml, p=0.002). N-terminal-pro brain natriuretic peptide increased in 16 (57.1%) men and 5 (26.3%) women (p=0.037). Five men (17.9%) had detected positive influenza A antibody, but no women. During 2-week admission, 5 (17.9%) men and 1 (5.3%) woman were reclassified into the critical type due to deterioration. Mortality was 3.6% in men and 0 in women respectively. Four (21.1%) women and one man (3.6%) recovered and discharged from hospital. Conclusion: Sex differences may exist in COVID-19 patients of severe type. Men are likely to have more complicated clinical condition and worse in-hospital outcomes as compared to women.

negative: Spreading of COVID-19 in Brazil: Impacts and uncertainties in social distancing strategies Brazil's continental dimension poses a challenge to the control of the spread of COVID-19. Due to the country specific scenario of high social and demographic heterogeneity, combined with limited testing capacity, lack of reliable data, under-reporting of cases, and restricted testing policy, the focus of this study is twofold: (i) to develop a generalized SEIRD model that implicitly takes into account the quarantine measures, and (ii) to estimate the response of the COVID-19 spread dynamics to perturbations/uncertainties. By investigating the projections of cumulative numbers of confirmed and death cases, as well as the effective reproduction number, we show that the model parameter related to social distancing measures is one of the most influential along all stages of the disease spread and the most influential after the infection peak. Due to such importance in the outcomes, different relaxation strategies of social distancing measures are investigated in order to determine which strategies are viable and less hazardous to the population. The results highlight the need of keeping social distancing policies to control the disease spread. Specifically, the considered scenario of abrupt social distancing relaxation implemented after the occurrence of the peak of positively diagnosed cases can prolong the epidemic, with a significant increase of the projected numbers of confirmed and death cases. An even worse scenario could occur if the quarantine relaxation policy is implemented before evidence of the epidemiological control, indicating the importance of the proper choice of when to start relaxing social distancing measures.

negative: Sunlight exposure increased Covid-19 recovery rates: A study in the central pandemic area of Indonesia This study aims to present the correlation between sunlight exposure and Covid-19 statuses in Jakarta, Indonesia. The secondary data analysis was derived from surveillance data for Covid-19 from government authorities, including the Ministry of Health, the Meteorological, Climatological, and Geophysical Agency, and the local government of Jakarta. Three statuses related to Covid-19 were examined in the study: incidence, death, and recovered. Meanwhile, sunlight exposure was presented as daily duration of it. Only the number of recovered patients correlated significantly with sunlight exposure (p-value = .025; r = 0.350). This study's findings showed that sunlight exposure was associated with recovery from Covid-19.

negative: Extracting the effective contact rate of COVID-19 pandemic In the absence of any available vaccines or drugs, prevention of the spread of Coronavirus Disease 2019 (COVID-19) pandemic is being achieved by putting many mitigation measures in place. It is indispensable to have robust and reliable ways of evaluating the effectiveness of these measures. In this work, we assume that, at a very coarse-grained level of description, the overall effect of all the mitigation measures is that we can still describe the spread of the pandemic using the most basic Susceptible-Exposed-Infectious-Removed ($SEIR$) model but with an"effective contact rate"($\beta$) which is time-dependent. We then use the time series data of the number of infected individuals in the population to extract the instantaneous effective contact rate which is the result of various social interventions put in place. This approach has the potential to be significantly useful while evaluating the impact of mitigation measures on the spread of COVID-19 in near future.

negative: COVID-19 and off label use of drugs: an ethical viewpoint BACKGROUND: The COVID-19 outbreak is rapidly spread over the world and kills infected patients. There is no proven medication for its treatment, so, all of the medications used for treatment are considered to be off-label. Off-label uses are not under regulation in the outbreak because there is no specific regulation for this condition. OBJECTIVES: In this short communication we aim at describing two ways of off-label use as clinical practice or investigational use. Further, we will describe the third way of off-label use, we named it pseudo-research and then we will state the most possible ethical challenges of off-label use for better perceptions and responsibility. RESULTS: The WHO considers off-label uses as country-specific. All international regulatory bodies consider off-label prescription as the physician’s responsibility and legal by necessitating some requirements. There is no international guideline for regulating investigational off-label uses as clinical practice. CONCLUSION: There are different types of approaches, none of them is comprehensive and conclusive. Furthermore, respecting the four ethical principles necessitates codification and strict regulation of off-label uses either as clinical practice or investigational. Besides, compilation of a special guideline based on ethical principles especially non-maleficence and autonomy for investigational off-label uses in disasters is highly recommended.

negative: Viewpoint: COVID-19. This virus is not the real enemy, but our approach to it could be.

negative: Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.

negative: Building a COVID-19 Vulnerability Index COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Information regarding this particular disease is limited, however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful to help for outreach campaigns in mitigating the diseases worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model having varying levels of predictive effectiveness at the expense of ease of implementation.

negative: Screening for Active COVID-19 Infection and Immunization Status Prior to Biologic Therapy in IBD Patients at the Time of the Pandemic Outbreak Abstract Coronavirus disease 2019 has been recently classified as pandemic infection by the World Health Organization. Patients with inflammatory bowel disease (IBD) are invited to follow the national recommendations as any other person. It is unclear whether a more aggressive clinical course might develop in asymptomatic COVID-19 infected subjects during biological therapy and current evidence does not support treatment suspension. However, during pandemic, the start of treatment with immunosuppressive drugs and biologics should be postponed whenever possible and based on an individual risk assessment. When clinical conditions and the disease activity do not allow a treatment delay, before starting a biological therapy, screening of IBD patients for COVID-19 active infection by RT-PCR should be advisable, even in absence of clinical suspicion. Serum antibody testing, when available, could provide evidence of infection as well as identify patients already immune to the disease.

negative: Sindrome Takotsubo in corso di polmonite da SARS-CoV-2: una possibile complicanza cardiovascolare./ [Takotsubo syndrome during SARS-CoV-2 pneumonia: a possible cardiovascular complication] Takotsubo syndrome (TTS) is one of the causes of myocardial infarction with non-obstructive coronary arteries, and is often triggered by physical events (e.g. acute respiratory failure), or emotional events (e.g. loss of a family member, cardiac stress induced by an acute illness). SARS-CoV-2 pneumonia currently represents a worldwide health problem; the correlations between cardiovascular disease, myocardial injury and SARS-CoV-2 infection are still unclear, but initial data show that myocardial damage represents a negative prognostic factor. Myocardial injury during SARS-CoV-2, as defined by a pathological rise in circulating troponin levels, is not an uncommon complication in hospitalized patients, and is significantly more frequent in intensive care unit patients and among those who died. In this setting, myocardial injury is mainly secondary to type 2 myocardial infarction (mismatch in myocardial oxygen supply and demand during respiratory failure); other causes include myocarditis, coronary thrombosis, sepsis or septic shock. At present, only few cases of TTS have been described during SARS-CoV-2. Here we report the case of a patient hospitalized for pneumonia and respiratory failure due to SARS-CoV-2 with subsequent onset of TTS triggered by both physical and emotional events.

negative: Predictions, role of interventions and effects of a historic national lockdown in India's response to the COVID-19 pandemic: data science call to arms Importance: India has taken strong and early public health measures for arresting the spread of the COVID-19 epidemic. With only 536 COVID-19 cases and 11 fatalities, India - a democracy of 1.34 billion people - took the historic decision of a 21-day national lockdown on March 25. The lockdown was further extended to May 3, soon after the analysis of this paper was completed. Objective: To study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 cases in India compared to other less severe non-pharmaceutical interventions using epidemiological forecasting models and Bayesian estimation algorithms; to compare effects of hypothetical durations of lockdown from an epidemiological perspective; to study alternative explanations for slower growth rate of the virus outbreak in India, including exploring the association of the number of cases and average monthly temperature; and finally, to outline the pivotal role of reliable and transparent data, reproducible data science methods, tools and products as we reopen the country and prepare for a post lock-down phase of the pandemic. Design, Setting, and Participants: We use the daily data on the number of COVID-19 cases, of recovered and of deaths from March 1 until April 7, 2020 from the 2019 Novel Coronavirus Visual Dashboard operated by the Johns Hopkins University Center for Systems Science and Engineering (JHU CSSE). Additionally, we use COVID-19 incidence counts data from Kaggle and the monthly average temperature of major cities across the world from Wikipedia. Main Outcome and Measures: The current time-series data on daily proportions of cases and removed (recovered and death combined) from India are analyzed using an extended version of the standard SIR (susceptible, infected, and removed) model. The eSIR model incorporates time-varying transmission rates that help us predict the effect of lockdown compared to other hypothetical interventions on the number of cases at future time points. A Markov Chain Monte Carlo implementation of this model provided predicted proportions of the cases at future time points along with credible intervals (CI). Results: Our predicted cumulative number of COVID-19 cases in India on April 30 assuming a 1-week delay in people's adherence to a 21-day lockdown (March 25 - April 14) and a gradual, moderate resumption of daily activities after April 14 is 9,181 with upper 95% CI of 72,245. In comparison, the predicted cumulative number of cases under "no intervention" and "social distancing and travel bans without lockdown" are 358 thousand and 46 thousand (upper 95% CI of nearly 2.3 million and 0.3 million) respectively. An effective lockdown can prevent roughly 343 thousand (upper 95% CI 1.8 million) and 2.4 million (upper 95% CI 38.4 million) COVID-19 cases nationwide compared to social distancing alone by May 15 and June 15, respectively. When comparing a 21-day lockdown with a hypothetical lockdown of longer duration, we find that 28-, 42-, and 56-day lockdowns can approximately prevent 238 thousand (upper 95% CI 2.3 million), 622 thousand (upper 95% CI 4.3 million), 781 thousand (upper 95% CI 4.6 million) cases by June 15, respectively. We find some suggestive evidence that the COVID-19 incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with Pearson correlation estimates [95% confidence interval] between average monthly temperature and total monthly incidence around the world being -0.185 [-0.548, 0.236] for January, -0.110 [-0.362, 0.157] for February, and -0.173 [-0.314, -0.026] for March. Conclusions and Relevance: The lockdown, if implemented correctly in the end, has a high chance of reducing the total number of COVID-19 cases in the short term, and buy India invaluable time to prepare its healthcare and disease monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. We cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. From an epidemiological perspective, a longer lockdown between 42-56 days is preferable. However, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. Data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. Software: Our contribution to data science includes an interactive and dynamic app (covind19.org) with short- and long-term projections updated daily that can help inform policy and practice related to COVID-19 in India. Anyone can visualize the observed data for India and create predictions under hypothetical scenarios with quantification of uncertainties. We make our prediction codes freely available (https://github.com/umich-cphds/cov-ind-19) for reproducible science and for other COVID-19 affected countries to use them for their prediction and data visualization work.

negative: Stability of the COVID-19 virus under wet, dry and acidic conditions COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was ≤1.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.

negative: Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc) Abstract Background and aims Multiple issues in management of COVID have emerged, but confusion persists regarding rational interpretation. Aim of this brief review is to review these issues based on current literature. Methods This is a narrative review with Pubmed and Google Scholar search till 23 March 2020. Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease. Results We discuss evidence regarding role of chloroquine and hydroxychloroquine in treatment and prophylaxis, use of inhibitors of the renin angiotensin system, safety of ibuprofen, unusual clinical features like gastrointestinal symptoms and interpretation of tests for cardiac enzymes and biomarkers. Conclusions While our conclusions on management of COVID-19 patients with co-morbidities are based on current evidence, however, data is limited and there is immediate need for fast track research.

negative: The Radiology Department during the COVID-19 pandemic: a challenging, radical change

negative: Chest Radiographic and CT Findings of the 2019 Novel Coronavirus Disease (COVID-19): Analysis of Nine Patients Treated in Korea OBJECTIVE: This study presents a preliminary report on the chest radiographic and computed tomography (CT) findings of the 2019 novel coronavirus disease (COVID-19) pneumonia in Korea. MATERIALS AND METHODS: As part of a multi-institutional collaboration coordinated by the Korean Society of Thoracic Radiology, we collected nine patients with COVID-19 infections who had undergone chest radiography and CT scans. We analyzed the radiographic and CT findings of COVID-19 pneumonia at baseline. Fisher's exact test was used to compare CT findings depending on the shape of pulmonary lesions. RESULTS: Three of the nine patients (33.3%) had parenchymal abnormalities detected by chest radiography, and most of the abnormalities were peripheral consolidations. Chest CT images showed bilateral involvement in eight of the nine patients, and a unilobar reversed halo sign in the other patient. In total, 77 pulmonary lesions were found, including patchy lesions (39%), large confluent lesions (13%), and small nodular lesions (48%). The peripheral and posterior lung fields were involved in 78% and 67% of the lesions, respectively. The lesions were typically ill-defined and were composed of mixed ground-glass opacities and consolidation or pure ground-glass opacities. Patchy to confluent lesions were primarily distributed in the lower lobes (p = 0.040) and along the pleura (p < 0.001), whereas nodular lesions were primarily distributed along the bronchovascular bundles (p = 0.006). CONCLUSION: COVID-19 pneumonia in Korea primarily manifested as pure to mixed ground-glass opacities with a patchy to confluent or nodular shape in the bilateral peripheral posterior lungs. A considerable proportion of patients with COVID-19 pneumonia had normal chest radiographs.

negative: Detection of feline coronaviruses by culture and reverse transcriptase-polymerase chain reaction of blood samples from healthy cats and cats with clinical feline infectious peritonitis Abstract A reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of the feline coronavirus (FCoV) genome and a co-cultivation method for the isolation of field strains of FCoV are described. Using the RT-PCR assay to assess blood samples from cats with feline infectious peritonitis (FIP) (n=47) and healthy cats from households with endemic FCoV (n=69) it was shown that approximately 80% of the cats were viraemic, irrespective of their health status. It was also shown that, over a 12-month period, a similar percentage of healthy cats remained viraemic, and that the presence of viraemia did not appear to predispose the cats to the development of FIP. The co-cultivation system proved to be a suitable method for the culture of field strains of FCoV from blood samples, so long as the cultures were maintained for at least 4 weeks. Using this system, followed by the RT-PCR, viraemia was detected as frequently as by RT-PCR on RNA extracted directly from peripheral blood mononuclear cells.

negative: Therapeutic strategies for critically ill patients with COVID-19 Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.

negative: COVID-19: Magnifying the Effect of Health Disparities

negative: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R(2) = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t = −2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

negative: COVID-19 Related Loneliness and Psychiatric Symptoms among Older Adults: The Buffering Role of Subjective Age OBJECTIVES: The study examined whether subjective age moderated the relationship between loneliness due to the COVID-19 pandemic and psychiatric symptoms. METHODS: A convenience sample of older adult Israelis (N=277, mean age=69.58±6.72) completed web-based questionnaires comprising loneliness, anxiety, depressive and peritraumatic distress symptoms. They also reported how old they felt. RESULTS: The positive relationship between loneliness due to the COVID-19 pandemic and psychiatric symptoms was weak among those who felt younger than their age while this very same relationship was robust among those feeling older. CONCLUSIONS: Young subjective age may weaken the loneliness-symptom association among older adults during the COVID-19 pandemic. Older adults holding an older age identity are more susceptible to the adverse effects of loneliness. Although preliminary, the findings may inform screening and interventions. Subjective age may help identify those at high risk in suffering from loneliness, and suggest interventions aimed at ameliorating both loneliness and older subjective ages.

negative: COVID-19 and people who use drugs: a call for action

negative: Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval –10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.

negative: The Psychological Impact of COVID-19 on Chinese Individuals COVID-19 not only affects the physical health of Chinese people, but also their psychological health. This article mainly summarized the causes, clinical manifestations and preventive measures of COVID-19 impact on psychology of Chinese people, and presented two representative cases at the same time.

negative: Comparison of virus concentration methods for the RT-qPCR-based recovery of murine hepatitis virus, a surrogate for SARS-CoV-2 from untreated wastewater Abstract There is currently a clear benefit for many countries to utilize wastewater-based epidemiology (WBE) as part of ongoing measures to manage the coronavirus disease 2019 (COVID-19) global pandemic. Since most wastewater virus concentration methods were developed and validated for nonenveloped viruses, it is imperative to determine the efficiency of the most commonly used methods for the enveloped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Municipal wastewater seeded with a human coronavirus (CoV) surrogate, murine hepatitis virus (MHV), was used to test the efficiency of seven wastewater virus concentration methods: (A–C) adsorption-extraction with three different pre-treatment options, (D–E) centrifugal concentration device methods with two different devices, (F) polyethylene glycol (PEG 8000) concentration, and (G) ultrafiltration. MHV was quantified by reverse-transcription quantitative polymerase chain reaction and the concentration efficiency was calculated for each method. The mean MHV recoveries ranged from 26.7 to 65.7%. The most efficient methods were (B) Adsorption-extraction methods, with MgCl2 pre-treatment, and (C) without manipulation (C), most efficiently concentrated MHV. The third most efficient method used the Amicon® Ultra-15 centrifugal device (D) and its recovery efficiency was not statistically different from the most efficient methods. The methods with the worst recovery efficiency included the adsorption extraction method with acidification (A), followed by PEG concentration (F). Our results suggest that absorption-extraction methods with minimal pretreatment or without manipulation can provide suitably rapid, cost-effective and relatively straightforward recovery of enveloped viruses in wastewater. The MHV is a promising process control for SARS-CoV-2 surveillance and can be used as a quality control measure to support community-level epidemic mitigation and risk assessment.

negative: Repositionnement de la chlorpromazine dans le traitement du COVID-19: étude reCoVery Abstract OBJECTIVES: The ongoing COVID-19 pandemic comprises a total of more than 2 350 000 cases and 160 000 deaths. The interest in anti-coronavirus drug development has been limited so far and effective methods to prevent or treat coronavirus infections in humans are still lacking. Urgent action is needed to fight this fatal coronavirus infection by reducing the number of infected people along with the infection contagiousness and severity. Since the beginning of the COVID-19 outbreak several weeks ago, we observe in GHU PARIS Psychiatrie & Neurosciences (Sainte-Anne hospital, Paris, France) a lower prevalence of symptomatic and severe forms of COVID-19 infections in psychiatric patients (∼4 %) compared to health care professionals (∼14 %). Similar observations have been noted in other psychiatric units in France and abroad. Our hypothesis is that psychiatric patients could be protected from the severe form of COVID-19 by their psychotropic treatments. Chlorpromazine (CPZ) is a phenothiazine derivative widely used in clinical routine in the treatment of acute and chronic psychoses. This first antipsychotic medication has been discovered in 1952 by Jean Delay and Pierre Deniker at Sainte-Anne hospital. In addition to its antipsychotic effects, several in vitro studies have also demonstrated a CPZ antiviral activity via the inhibition of clathrin-mediated endocytosis. Recently, independent studies revealed that CPZ is an anti-MERS-CoV and an anti-SARS-CoV-1 drug. In comparison to other antiviral drugs, the main advantages of CPZ lie in its biodistribution: (i) preclinical and clinical studies have reported a high CPZ concentration in the lungs (20--200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (20-60 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms of COVID-19. METHODS: In this context, we will test the hypothesis that CPZ could decrease the unfavorable evolution of COVID-19 infection in oxygen-requiring patients without the need for intensive care, but also reduce the contagiousness of SARS-CoV-2. At this end, we designed a pilot, phase III, multicenter, single blind, randomized controlled therapeutic trial. Efficacy of CPZ will be assessed according to clinical, biological and radiological criteria. The main objective is to demonstrate a shorter Time To Response (TTR) to treatment in the CPZ + standard-of-care (CPZ + SOC) group, compared to the SOC group. Response to treatment is defined by a reduction of at least one level of severity on the WHO-Ordinal Scale for Clinical Improvement (WHO-OSCI). The secondary objectives are to demonstrate in the CPZ + SOC group, compared to the SOC group: A) superior clinical improvement; B) a greater decrease in the biological markers of viral attack by SARS-CoV-2 (PCR, viral load); C) a greater decrease in inflammatory markers (e.g. CRP and lymphopenia); D) a greater decrease in parenchymal involvement (chest CT) on the seventh day post-randomization; E) to define the optimal dosage of CPZ and its tolerance; F) to evaluate the biological parameters of response to treatment, in particular the involvement of inflammatory cytokines. Patient recruitment along with the main and secondary objectives are in line with WHO 2020 COVID-19 guidelines. CONCLUSION: This repositioning of CPZ as anti-SARS-CoV-2 activity offers an alternative and rapid strategy to alleviate the virus propagation and the infection severity and lethality. This CPZ repositioning strategy also avoids numerous developmental and experimental steps, can save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easy to manage side effects. Indeed, CPZ is an FDA-approved drug with an excellent tolerance profile, prescribed for around 70 years, in psychiatry but also in clinical routine in nausea and vomiting of pregnancy, in advanced cancer and also to treat headaches in various neurological conditions. The broad spectrum of CPZ treatment - including antipsychotic, anxiolytic, antiemetic, antiviral, immunomodulatory effects along with inhibition of clathrin-mediated endocytosis and modulation of blood-brain barrier - is in line with the historical French commercial name for CPZ, i.e. LARGACTIL, chosen as a reference to its 'LARGe ACTion' properties. The discovery of those CPZ properties, as for many other molecules in psychiatry, is both the result of serendipity and careful clinical observations. Using this approach, the field of mental illness could provide innovative therapeutic approaches to fight SARS-CoV-2.

negative: The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19 Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. This may be driven by direct endothelial cell entry by the virus, or indirectly by activated inflammatory cascade. Major risk groups identified for adverse outcomes in COVID-19 are diabetes, and those from the Black, Asian and ethnic minority (BAME) populations. Hyperglycaemia (expressed as glycated haemoglobin or mean hospital glucose) correlates with worse outcomes in COVID-19. It is not known whether hyperglycaemia is causative or is a surrogate marker - persistent hyperglycaemia is well known as an aetiological agent in microangiopathy. In this article, we propose that pre-existing endothelial dysfunction of microangiopathy, more commonly evident in diabetes and BAME groups, makes an individual vulnerable to the subsequent ‘endothelitis’ of COVID-19 infection.

negative: Are we there yet? The transition from response to recovery for the COVID-19 pandemic Abstract There is no corner of the planet that has not been impacted by the rapid spread of the novel coronavirus, COVID-19. While the COVID-19 pandemic has already had far-reaching socioeconomic consequences commonly associated with natural hazards (such as disruption to society, economic damage, and loss of lives), the response of governments around the world has been unparalleled and unlike anything seen before. Governments are faced with a myriad of multi-dimensional effects of the pandemic, including direct impacts on public health systems and population health and indirect socioeconomic effects including disruption to every single sector of the economy and mass unemployment. There is, additionally, the growing realisation that the timescale associated with this crisis may permanently change the very foundations of societies ‘normal’ day-to-day life. As the world transitions to recovering from COVID-19, those developing that recovery need support in adjusting and improving their policies and measures. The situation seems dire, the stakes are high. Literature about the transition between the response and recovery phase in relation to pandemics is scarce. Further complication is that the pandemic will not allow countries to simply transition to the full-scale recovery, instead, a rebound from recovery to response phase is expected for a certain period until the immunization is in place. Pandemics indeed force us to think beyond typical emergency management structures; the cycles of the disaster risk management in the case of biological and other natural hazards are not exactly the same and no one-size-fits-all approach may be used. Still, some parallels may be drawn with the efforts to combat natural hazards and some lessons may be used from previous and the current pandemic. Based on these experiences and reflections, this paper provides a set of policy directions to be considered during the transition towards, as well as throughout, this transition phase. It is suggested that meeting this global, multi-dimensional, and complex challenge will require considerable international collaboration (even convention) and macro-scale changes to global and national policies. The recovery issues are mainly going to be dominated by politics, economics and social science. Necessary for an effective recovery, the pandemic response needs to be a holistic response, combined with an improved data ecosystem between the public health system and the community. We should also view this outbreak and our response to it as an opportunity to learn lessons and reaffirm our universal commitment to sustainable development and enhancing wellbeing around the world.

negative: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death

negative: The role of cardiac imaging in hospitalized COVID-19-positive patients COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.

negative: Assessing resilience of healthcare infrastructure exposed to COVID-19: emerging risks, resilience indicators, interdependencies and international standards In the moment of preparation of this paper, the world is still globally in grip of the Corona (COVID-19) crisis, and the need to understand the broader overall framework of the crisis increases. As in similar cases in the past, also with this one, the main interest is on the “first response”. Fully appreciating the efforts of those risking their lives facing pandemics, this paper tries to identify the main elements of the larger, possibly global, framework, supported by international standards, needed to deal with new (emerging) risks resulting from threats like Corona and assess the resilience of systems affected. The paper proposes that future solutions should include a number of new elements, related to both risk and resilience. That should include broadening the scope of attention, currently focused onto preparation and response phases, to the phases of “understanding risks”, including emerging risks, and transformation and adaptation. The paper suggests to use resilience indicators in this process. The proposed approach has been applied in different cases involving critical infrastructures in Europe (energy supply, water supply, transportation, etc., exposed to various threats), including the health system in Austria. The detailed, indicator-based, resilience analysis included mapping resilience, resilience stress-testing, visualization, etc., showing, already before the COVID-19, the resilience (stress-testing) limits of the infrastructures. A simpler (57 indicator based) analysis has, then been done for 11 countries (including Austria). The paper links these results with the options available in the area of policies, standards, guidelines and tools (such as the RiskRadar), with focus on interdependencies and global standards—especially the new ISO 31,050, linking emerging risks and resilience.

negative: Time series modelling to forecast the confirmed and recovered cases of COVID-19 Coronaviruses are enveloped RNA viruses from the Coronaviridae family affecting neurological, gastrointestinal, hepatic and respiratory systems. In late 2019 a new member of this family belonging to the Betacoronavirus genera (referred to as COVID-19) originated and spread quickly across the world calling for strict containment plans and policies. In most countries in the world, the outbreak of the disease has been serious and the number of confirmed COVID-19 cases has increased daily, while, fortunately the recovered COVID-19 cases have also increased. Clearly, forecasting the “confirmed” and “recovered” COVID-19 cases helps planning to control the disease and plan for utilization of health care resources. Time series models based on statistical methodology are useful to model time-indexed data and for forecasting. Autoregressive time series models based on two-piece scale mixture normal distributions, called TP–SMN–AR models, is a flexible family of models involving many classical symmetric/asymmetric and light/heavy tailed autoregressive models. In this paper, we use this family of models to analyze the real world time series data of confirmed and recovered COVID-19 cases.

negative: One size does not fit all – Patterns of vulnerability and resilience in the COVID-19 pandemic and why heterogeneity of disease matters

negative: Cardiovascular disease potentially contributes to the progression and poor prognosis of COVID-19 Abstract Background A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), outbroke in Wuhan, China in December 2019, and spread all over the world. Patients with COVID-19 showed huge differences in the hospital stays, progression and prognosis. As reported, the comorbidities may play an important role in COVID-19. Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19. Methods 83 confirmed COVID-19 patients were divided into the CVD (n=42) and non-CVD (n=41) group according to their medical history. Medical records information including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT) as well as treatment measures were collected, analyzed and compared between two groups. Results COVID-19 patients with CVD showed: (1) more severe pathological changes in the lung, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK) and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD. Conclusions Our data indicated that CVD is a strong risk factor for a rapid progression and bad prognosis of COVID-19. More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.

negative: Persistent infections support maintenance of a coronavirus in a population of Australian bats (Myotis macropus) Understanding viral transmission dynamics within populations of reservoir hosts can facilitate greater knowledge of the spillover of emerging infectious diseases. While bat-borne viruses are of concern to public health, investigations into their dynamics have been limited by a lack of longitudinal data from individual bats. Here, we examine capture–mark–recapture (CMR) data from a species of Australian bat (Myotis macropus) infected with a putative novel Alphacoronavirus within a Bayesian framework. Then, we developed epidemic models to estimate the effect of persistently infectious individuals (which shed viruses for extensive periods) on the probability of viral maintenance within the study population. We found that the CMR data analysis supported grouping of infectious bats into persistently and transiently infectious bats. Maintenance of coronavirus within the study population was more likely in an epidemic model that included both persistently and transiently infectious bats, compared with the epidemic model with non-grouping of bats. These findings, using rare CMR data from longitudinal samples of individual bats, increase our understanding of transmission dynamics of bat viral infectious diseases.

negative: Model the transmission dynamics of COVID-19 propagation with public health intervention In this work, a researcher develop $SHEIQRD$ (Susceptible-Stay at home-Exposed-Infected-Quarantine-Recovery-Death) coronavirus pandemic spread model. The disease-free and endemic equilibrium points are calculated and analyzed. The basic reproductive number $R_0$ is derived and its sensitivity analysis is done. COVID-19 pandemic spread is die out when $R_0\leq 1$ and its persist in the community whenever $R_0>1$. Efficient stay at home rate, high coverage of precise identification and isolation of expose and infected individuals, and redaction of transmission and stay at home return rate can be mitigate the pandemics. Finally, theoretical analysis and numerical results are consistent.

negative: A Tale of Two Communities: Characterizing Reddit Response to COVID-19 through /r/China_Flu and /r/Coronavirus The COVID-19 pandemic has deeply impacted people's lives around the globe. During the extended lockdowns caused by the pandemic, online communities are crucial for people to access information and share experiences. In particular, two"new"communities have emerged on Reddit: /r/China_flu and /r/Coronavirus. By studying activities and users in these two communities, we provide a characterization of people's responses to COVID-19 on Reddit. First, we find that user activity peaks around March 17, when the World Health Organization (WHO) announced COVID-19 as a pandemic. Shortly after that, the activity levels of both communities have been declining week by week. We further illustrate the central role of these two communities in the emergence of COVID-related communities. Second, we study the differences between these two communities. /r/Coronavirus is recommended as the official community for COVID-19 on Reddit, while /r/China_flu adopts a loose moderation practice. As a result, we observe that these two communities are gradually growing apart and more extremism is being found in /r/China_flu. Finally, we examine the spillover effect of the COVID-19 pandemic on user activity across the entire Reddit platform. Our results show significant changes in user activities outside COVID-related communities. In subreddits related to finance, food, and countries/cities, user activity is recovering to the pre-pandemic level in late April and May as countries reopen, but subreddits related to travel and sports remain highly impacted and show lower activity levels than the pre-pandemic period. Our work highlights the strength of Reddit as a source for understanding public reactions to COVID-19 and the importance of content moderation on the Internet during a pandemic.

negative: Long-Term Outcomes After Open Repair for Ruptured Abdominal Aortic Aneurysm BACKGROUND: Early mortality in ruptured abdominal aneurysm (rAAA) is high, but data on long-term outcome are scarce. The aim of this study was to investigate the long-term outcome in survivors after open surgery for rAAA in well-defined population. METHODS: This is a population-based, observational long-term follow-up (beyond 30-day mortality) study of patients surgically treated for rAAA from 2000 through 2014. Long-term survival was analysed using Kaplan–Meier estimates and compared to the general population by analyses of relative survival. RESULTS: Out of 178 patients operated for rAAA, 95 patients (55%) either died in the perioperative period, were referred from other hospitals or were lost to follow-up (two patients). Altogether 83 patients were eligible for long-term outcomes: 72 men and 11 women. Estimated median crude survival time was 6.5 years [95% confidence interval (CI) 4.8–8.2]. Men had a median survival of 7.3 years (95% CI 5.1–9.4) versus 5.4 years in females (95% CI 3.5–7.3) (P = 0.082). Reinterventions during follow-up occurred in 31 (37%). Relative survival demonstrated a slightly higher risk of death in the rAAA population compared to the general age- and gender-matched population. Age, but not comorbidities, had a significant influence on long-term survival. CONCLUSION: For survivors beyond 30 days after surgery for rAAA, long-term survival compares well to that of an age- and sex-matched population. A high frequency of cardiovascular comorbidities did not seem to affect long-term survival.

negative: Outcome of coronavirus‐associated severe acute respiratory syndrome using a standard treatment protocol Objective: There is so far no consensus on the optimal treatment strategy for the coronavirus‐associated severe acute respiratory syndrome (SARS). We aimed to analyse the outcomes of a standard treatment strategy comprising antibiotics, a combination of ribavirin, a 3‐week step‐down course of corticosteroids, and the possibility of pulsed methylprednisolone rescue in the event of deterioration. Methodology: This was a prospective cohort study performed at a major public‐funded hospital in Hong Kong. Eighty‐eight World Health Organisation/Centers for Disease Control and Prevention probable cases of SARS (97% laboratory‐confirmed) were treated with a standard protocol previously reported. Seventy‐one patients treated de novo were analysed in detail with regard to time to clinical stabilization after combination treatment, requirement of additional therapy (pulsed methylprednisolone; assisted ventilation); and final outcomes (recovery, mortality). Results: The mean age was 42. Twenty‐one patients (24%) had comorbidities. Three of 71 treated de novo recovered with antibiotics alone. The remaining 68 received combination treatment at a mean of 5.8 days after symptom onset, of whom 30 subsequently required pulsed methylprednisolone rescue (independent predictors: older age and higher LDH) and 18 required assisted ventilation (independent predictors: older age, higher oxygen requirement and creatinine level). Their median time to clinical stabilization was 8.0 days after combination treatment (independent predictor for longer time to stabilization: median age of 41 or above). Common complications were hyperglycaemia (58%), pneumo‐mediastinum/thoraces (13%), psychiatric manifestations (7%) and ventilator‐associated pneumonia (2%). One patient (1%) died of SARS‐related respiratory failure. All‐cause mortality was 3.4%, occurring in patients aged > 65 years only. None of the discharged survivors required continuation of oxygen therapy. Conclusions: This standard treatment protocol resulted in overall satisfactory outcomes. Randomized controlled trial is suggested to confirm its efficacy.

negative: Predictions for COVID-19 outbreak in India using Epidemiological models COVID-19 data from India is compared against several countries as well as key states in the US with a major outbreak, and it is found that the basic reproduction number R_0 for India is in the expected range of 1.4-3.9. Further, the rate of growth of infections in India is very close to that in Washington and California. Exponential and classic susceptible-infected-recovered (SIR) models based on available data are used to make short and long-term predictions on a daily basis. Based on the SIR model, it is estimated that India will enter equilibrium by the end of May 2020 with the final epidemic size of approximately 13,000. However, this estimation will be invalid if India enters the stage of community transmission. The impact of social distancing, again with the assumption of no community transmission, is also assessed by comparing data from different geographical locations.

negative: Can the COVID-19 epidemic be controlled on the basis of daily test reports? This paper studies if and to which extent COVID-19 epidemics can be controlled by authorities taking decisions on public health measures on the basis of daily reports of swab test results, active cases and total cases. A suitably simplified process model is derived to support the controllability analysis, highlighting the presence of very significant time delay; the model is validated with data from several outbreaks. The analysis shows that suppression strategies can be effective if strong enough and enacted early on. It also shows how mitigation strategies can fail because of the combination of delay, unstable dynamics, and uncertainty in the feedback loop; approximate conditions based on the theory of limitation of linear control are given for feedback control to be feasible.

negative: Understand Research Hotspots Surrounding COVID-19 and Other Coronavirus Infections Using Topic Modeling Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that causes severe respiratory illness in humans, which eventually results in the current outbreak of novel coronavirus disease (COVID-19) around the world. The research community is interested to know what are the hotspots in coronavirus (CoV) research and how much is known about COVID-19. This study aimed to evaluate the characteristics of publications involving coronaviruses as well as COVID-19 by using a topic modeling analysis. Methods: We extracted all abstracts and retained the most informative words from the COVID-19 Open Research Dataset, which contains all the 35,092 pieces of coronavirus related literature published up to March 20, 2020. Using Latent Dirichlet Allocation modeling, we trained an eight-topic model from the corpus. We then analyzed the semantic relationships between topics and compared the topic distribution between COVID-19 and other CoV infections. Results: Eight topics emerged overall: clinical characterization, pathogenesis research, therapeutics research, epidemiological study, virus transmission, vaccines research, virus diagnostics, and viral genomics. It was observed that COVID-19 research puts more emphasis on clinical characterization, epidemiological study, and virus transmission at present. In contrast, topics about diagnostics, therapeutics, vaccines, genomics and pathogenesis only accounted for less than 10% or even 4% of all the COVID-19 publications, much lower than those of other CoV infections. Conclusions: These results identified knowledge gaps in the area of COVID-19 and offered directions for future research. Keywords: COVID-19, coronavirus, topic modeling, hotspots, text mining

negative: Survival analysis of hospital length of stay of novel coronavirus (COVID-19) pneumonia patients in Sichuan, China Objective Allocation of medical resource is essential to a strong public health system in response to COVID-19. Analysis of confirmed COVID-19 patients' hospital length of stay in Sichuan can be informative to decision-making in other regions of the world. Design A retrospective cross-sectional study. Data and Method Data from confirmed COVID-19 cases in Sichuan Province were obtained from the National Notifiable Diseases Reporting System (NNDRS) and field survey. We collected information on demographic, epidemiological, clinical characteristics, and the length of hospital stay for confirmed patients. We conducted an exploratory analysis using adjusted multivariate cox-proportional models. Participants A total of 538 confirmed patients of COVID-19 infection in Sichuan Province from January to March 2020. Outcome measure The length of hospital stay after admissions for confirmed patients. Results From January 16, 2020 to March 4, 2020, 538 human cases of COVID-19 infection were laboratory-confirmed, and were hospitalized for treatment. Among these, 271 (50%) were 45 years of age or above, 285 (53%) were male, 450 (84%) were considered as having mild symptoms. The median hospital length of stay was 19 days (interquartile range (IQR): 14-23, Range: 3-41). Adjusted multivariate analysis showed that longer hospital length of stay was associated with factors aged 45 and over (HR: 0.74, 95% CI: 0.60-0.91), those admitted to provincial hospital (HR: 0.73, 95% CI: 0.54-0.99), and those with serious illness (HR: 0.66, 95% CI: 0.48-0.90); living in areas with more than 5.5 healthcare workers per 1000 population (HR: 1.32, 95% CI: 1.05-1.65) was associated with shorter hospital length of stay. There was no gender difference. Conclusions Preparation control measures of COVID-19 should involve the allocation of sufficient medical resources, especially in areas with older vulnerable populations and in areas that lack basic medical resources.

negative: Viral-associated exacerbations of asthma and COPD Exacerbations of asthma and chronic obstructive pulmonary disease are major burdens on the healthcare system, and contribute significantly to the mortality and morbidity associated with these diseases. Upper respiratory viral infections are associated with the majority of such disease exacerbations. The past few years have seen advances in the mechanisms by which viral infections induce pro-inflammatory chemokine production, and in our understanding of host antiviral and anti-inflammatory defence pathways that might regulate responses to infection. A more comprehensive understanding of the molecular basis of these processes could elucidate new therapeutic approaches to reduce the devastating impact that these exacerbations have on quality of life and healthcare costs.

negative: Critical patients with coronavirus disease 2019: Risk factors and outcome nomogram

negative: Participation of the nursing workforce to address COVID-19 among people who use alcohol, tobacco, and drugs

negative: The current understanding and potential therapeutic options to combat COVID-19 Abstract The ongoing wreaking global outbreak of the novel human beta coronavirus (CoV) pathogen was presumed to be from a seafood wholesale market in Wuhan, China, belongs to the Coronaviridae family in the Nidovirales order. The virus is highly contagious with potential human-human transmission which was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread across six continents and emerged as a global pandemic in short span with alarming levels of spread and severity. This virus associated symptoms and infectious respiratory illness is designated as coronavirus disease 19 (COVID-19). The SARS-CoV-2 possesses enveloped club-like spike protein projections with positive-sense large RNA genome and has a unique replication strategy. This virus was believed to have zoonotic origin with genetical identity to bat and pangolin CoV. In the current review, we introduce a general overview about the human CoVs and the associated diseases, the origin, structure, replication and key clinical events that occur in the COVID-19 pathogenicity. Furthermore, we focused on possible therapeutic options such as repurposing drugs including antimalarials, antivirals, antiparasitic drugs, and anti-HIV drugs, as well as monoclonal antibodies, vaccines as potential treatment options. Also we have summarized the latest research progress on the usage of stem cell therapy, human convalescent serum, interferon's, in the treatment of COVID-19.

negative: Teicoplanin: an alternative drug for the treatment of COVID-19? In December 2019, a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China causing pneumonia outbreaks, first in the Wuhan region of China and then spread worldwide because of its probable high transmission efficiency. Owing to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find a therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin and ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococcal infections, previously showed efficacy to inhibit the first stage of the Middle East respiratory syndrome coronavirus (MERS-CoV) viral life cycle in human cells. This activity is conserved against SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

negative: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus A pandemic of a novel Coronavirus emerged in December of 2019 (COVID-19), causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antivirals, strategies for controlling and mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation, and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of the aforementioned control and mitigation strategies. Rigorous analysis of the model shows that the disease-free equilibrium is locally-asymptotically stable if a certain epidemiological threshold, known as the reproduction number (denoted by [Formula: see text]), is less than unity. Simulations of the model, using data relevant to COVID-19 transmission dynamics in the US state of New York and the entire US, show that the pandemic burden will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. The duration and timing of the relaxation or termination of the strict social-distancing measures are crucially-important in determining the future trajectory of the COVID-19 pandemic. This study shows that early termination of the strict social-distancing measures could trigger a devastating second wave with burden similar to those projected before the onset of the strict social-distancing measures were implemented. The use of efficacious face-masks (such as surgical masks, with estimated efficacy [Formula: see text] 70%) in public could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks in public consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of estimated efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of the other anti-COVID-19 intervention strategies can lead to the elimination of the pandemic. This study emphasizes the important role social-distancing plays in curtailing the burden of COVID-19. Increases in the adherence level of social-distancing protocols result in dramatic reduction of the burden of the pandemic, and the timely implementation of social-distancing measures in numerous states of the US may have averted a catastrophic outcome with respect to the burden of COVID-19. Using face-masks in public (including the low efficacy cloth masks) is very useful in minimizing community transmission and burden of COVID-19, provided their coverage level is high. The masks coverage needed to eliminate COVID-19 decreases if the masks-based intervention is combined with the strict social-distancing strategy.

negative: Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries Abstract Background and aims No drugs are currently approved for Coronavirus Disease-2019 (COVID-19), although some have been tried. In view of recent studies and discussion on chloroquine and hydroxychloroquine (HCQ), we aimed to review existing literature and relevant websites regarding these drugs and COVID-19, adverse effects related to drugs, and related guidelines. Aims and methods We systematically searched the PubMed database up till March 21, 2020 and retrieved all the articles published on chloroquine and HCQ and COVID-19. Results Two small human studies have been conducted with both these drugs in COVID-19, and have shown significant improvement in some parameters in patients with COVID-19. Conclusion Considering minimal risk upon use, a long experience of use in other diseases, cost-effectiveness and easy availability across India, we propose that both these drugs are worthy of fast track clinical trial for treatment, and may be carefully considered for clinical use as experimental drugs. Since HCQ has been approved for treatment of diabetes in India, it should be further researched in diabetes and COVID-19, a subgroup where significant mortality has been shown.

negative: The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence Abstract The outbreak of emerging infectious pneumonia caused by 2019 Novel Coronavirus (2019-nCoV) has posed an enormous threat to public health, and traditional Chinese medicine (TCM) have made vast contribution to the prevention, treatment and rehabilitation of coronavirus disease 19 (COVID-19) among Chinese population. As an indispensable part of TCM, Chinese patent medicines (CPMs) are highly valued and critically acclaimed in their campaign to contain and tackle the epidemic, they can achieve considerable effects for both suspected cases under medical observation period, and confirmed individuals with serious underlying diseases or critical conditions. Given this, based on the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 in China, the present review summarized the basic information, clinical evidence and published literatures of recommended CPMs against COVID-19. The details were thoroughly introduced involving compositions, therapeutic effects, clinical indications, medication history of CPMs and the profiles of corresponding research. With regard to infected patients with different stages and syndrome, the preferable potentials and therapeutic mechanism of CPMs were addressed through the comprehensive collection of relevant literatures and on-going clinical trials. This study could provide an insight into clinical application and underlying mechanism of recommended CPMs against COVID-19, with the aim to share the Chinese experience in clinical practice and facilitate scientific development of TCM, especially CPMs in the fierce battle of COVID-19.

negative: COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.

negative: Management of Pemphigus in COVID-19 Pandemic Era; a Review Article The novel coronavirus is rapidly spreading around the world. Since the public announcement of the COVID-19 outbreak, several concerns have been raised by dermatologists as well as pemphigus patients who take immunosuppressive drugs. In this paper, we review the literature about the common treatment of pemphigus with a focus on the lessons from similar epidemics to find a proper suggestion to manage pemphigus in the COVID-19 pandemic era. The effect of many of the drugs used for treatment of Pemphigus vulgaris (PV) on COVID-19 is not clear. We also do not have data on the impact of this autoimmune disease, which may involve the mucous membranes, on the acquisition or course of COVID-19. We are currently in the midst of a pandemic and evaluating the effect of COVID-19 on the population of susceptible patients suffering from auto-immune diseases like pemphigus is essential. The evidence on best ways to manage patients with underlying conditions, such as pemphigus, during the outbreak of COVID-19 is evolving and the data is updated every day.

negative: Mental health status among family members of health care workers in Ningbo, China during the Coronavirus Disease 2019 (COVID-19) outbreak: a Cross-sectional Study Background: So far, the psychological impact of COVID-19 epidemic among family members of Health care workers (HCWs) in China has been neglected. The present cross-sectional study aimed to investigate the mental health status and related factors of families of HCWs in Designated Hospitals in Ningbo, China. Method: Family members of HCWs working in five designated hospitals in Ningbo, China were recruited between February 10th and 20th, 2020. Information on demographic variables, the COVID-19-related events in the lives, knowledge of COVID-19 and the working status of family members (that is, HCWs) was collected using online self-administered questionnaires. The mental health status were assessed using the Chinese version of Patient Health Questionnare-9 (PHQ-9) and Chinese version of Generalized Anxiety Disorder-7 (GAD-7 ). Multivariable logistic regression analyses were conducted to identify the main factors associated with the mental health conditions. Results: A total of 822 participants completed questionnaires correctly. (response rate of 95.80% ). The overall prevalence of GAD and depressive symptoms were 33.73%, and 29.35%, respectively. More times (hours) to focus on the COVID-19 (OR=1.215, 95%CI:1.061-1.391), family members (that is, HCWs) directly contact with confirmed or suspected COVID-19 patients (OR=1.477, 95%CI:1.069-2.040) were risk factors for GAD, while higher participants self-reported safety score for protective equipment of HCWs (OR=0.807, 95%CI:0.700-0.930) was a protective factor. More times (hours) to focus on the COVID-19 (OR=1.215, 95%CI:1.061-1.391), longer average working times per week for family members (that is, HCWs) (OR=1.017, 95%CI:1.005-1.029), being parents and other next of kin of HCWs were risk factors for depressive symptoms (OR=3.526, 95%CI:1.609-7.728 and OR=1.639, 95%CI:1.096-2.451, respectively). In addition, compared with participants who were HCWs, participants who were enterprise workers and were more likely to develop depressive symptoms(OR=1.750, 95%CI:1.104-2.776), while who were government employees or institutions employees were less likely to suffer depressive symptoms (OR=0.529, 95%CI:0.286-0.977). Conclusions: Psychological responses to COVID-19 have been dramatic among family members of HCWs during the rising phase of the outbreak. Our findings provide strong evidence to pay more attention on the mental health status of this vulnerable but often unseen populations during COVID-19 epidemic.

negative: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection [Image: see text] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is ∼2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.

negative: Demographic and Clinical Characteristics of the Severe Covid-19 Infections: First Report from Mashhad University of Medical Sciences, Iran Purpose. To report a comparison between fatalities and recovery of the severe Covid-19 infected patients based on demographic and clinical characteristics. Methods. Between 5 March and 12 May 2020, of 4,000 patients, 1,278 were laboratory confirmed to be Covid-19 infection in Mashhad, Iran. Finally, 334 deceased and 733 recovered cases were assessed in terms of demography, exposure history, health outcomes and clinical symptoms. Results. Mean (SD) age for confirmed patients, for deceased cases and for recovered cases. Mean (SD) age for all confirmed-patients was 56.9 (18.74), for the fatalities 67.26 (15.77) and for those recovered 52.82 (17.91) years. The rise of the mortality rate in relation to seniority was statistically significant. Despite a high frequency of Covid-19 infections accrued in the age groups of 30-39 and 40-49 years, most of these cases (88.2 and 85.8%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (9) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Fever (63.8%), cough (68.1%), and dyspnoea (72.7%) were the most frequent clinical symptoms. 5.2% of infected-cases were healthcare workers that two (3%) of them died. Most patients (48%) received both antiviral and antibiotic therapy. The mortality rate of Kaletra combination prescribed for severe cases was 46.7%. Conclusions. The characteristics of Covid-19 varied from died to survived infected patients. There were a higher number of fatalities in younger patients than in international studies. Diabetes and cardiovascular disorders were most prevalent co-morbidities. The study could not address the case-fatality rate of Covid-19 infection that remains for future studies.

negative: Frequency of testing for COVID 19 infection and the presence of higher number of available beds per country predict outcomes with the infection, not the GDP of the country - A descriptive statistical analysis Introduction: The novel coronavirus epidemic which originated in late 2019 from China has wreaked havoc on millions across the world with illness, death and socioeconomic recession. As of now no valid treatment or preventative strategy has evolved worldwide and governments across the world have been forced to take the draconian step of social isolation in communities by enforcing lockdowns. Aim of this Study: This study aims to correlate the rates of infection with the novel coronavirus and total deaths as the primary output variable. In addition the strength of association between infection rates and total death in comparison to GDP share of the respective countries, physicians, hospital beds and rates of testing for COVID 19 infection per thousand patients, is being assessed, in a bid to develop a model which would help to develop tools to reduce the impact of this disease. Material & Methods Data relating to number of cases, severity, cases recovered and deaths worldwide and specifically for the top six countries affected was collected from the WHO COVID-19 situation report which is being updated on a daily basis till 22nd March 2020, the date of analysis. Additional data related to GDP, physician and hospital bed per 1000 patients were procured from the World Bank database. All data were collected in a file in CSV format. Analysis was conducted in Jupyter notebook with Python 3.8.2 software and also with XL-Stat statistical software for excel. The analytical strategy was descriptive with no inferential overtones. Results: COVID 19 infection strongly correlates with total deaths (r : 0.89), with a predicted death rate of 25 patients per 1000 affected. There was no correlation between the GDP growth of the country and number of treating physicians/1000 patient population with any COVID 19 related outcome. However there was a negative correlation between COVID 19-related deaths and the number of beds available per 1000 population [r=-0.34]. Importantly there is an inverse correlation between the number of tests conducted per million population with the rates of active infections [r=-0.12] , new cases [r=-0.38] and new deaths [r=-0.28] in COVID 19. Conclusion: This is the first study to assess parameters other than age and sex and sets out a robust dataset which indicates an increased risk of worsening outcomes with lesser number of beds and testing, suggesting that the need of the hour is to increase available bed numbers and to increase rates of testing.

negative: COVID-19: is there a role for immunonutrition, particularly in the over 65s? In late December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei, China, resulting in the potentially fatal COVID-19. It went on to be officially recognised as a pandemic by the World Health Organisation on 11 March 2020. While many public health strategies have evolved, there has been little mention of the immune system and how this could be strengthened to help protect against viral infections such as SARS-CoV-2. The present paper evaluates the current evidence base relating to immunonutrition, with a particular focus on respiratory viruses. Within the nutrition sector a promising body of evidence studying inter-relationships between certain nutrients and immune competence already exists. This could potentially be an important player in helping the body to deal with the coronavirus, especially among elders. Evidence for vitamins C, D and zinc and their roles in preventing pneumonia and respiratory infections (vitamins C and D) and reinforcing immunity (zinc) appears to look particularly promising. Ongoing research within this important field is urgently needed.

negative: Coronavirus Disease 2019 in Geriatrics and Long-term Care: The ABCDs of COVID-19. The pandemic of coronavirus disease of 2019 (COVID-19) has global impact unseen since the 1918 worldwide influenza epidemic. All aspects of life have changed dramatically for now. The group most susceptible to COVID-19 are older adults and those with chronic underlying chronic medical disorders. The population residing in long-term care facilities generally are those who are both old and suffering from multiple comorbidities. In this article we provide information, insights, and recommended approaches to COVID-19 in the long-term facility setting. Since the situation is fluid and changing rapidly, readers are encouraged to access the resources cited in this article frequently. This article is protected by copyright. All rights reserved.

negative: COVID-19 and Diabetes: Knowledge in Progress Abstract Aims We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. Methods We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “incubation period”, “transmission”, “clinical features”, “diagnosis”, “treatment”, “diabetes”, with interposition of the Boolean operator “AND”. Results The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Conclusions Suggestions are made on the possible pathological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.

negative: Covid-19 Crisis Triage - Optimizing Health Outcomes and Disability Rights

negative: How to differentiate COVID-19 pneumonia from heart failure with computed tomography at initial medical contact during epidemic period OBJECTIVES To compare chest CT findings in heart failure with those of Corona Virus Disease 2019 (COVID-19) pneumonia. BACKGROUND During epidemic period, chest computed tomography (CT) has been highly recommended for screening patients with suspected COVID-19. However, the comparison of CT imaging between heart failure and COVID-19 pneumonia has not been fully elucidated. METHODS Patients with heart failure (n=12), COVID-19 pneumonia (n=12) and one patient with both diseases were retrospectively enrolled. Clinical information and imaging of chest CT were collected and analyzed. RESULTS There was no difference of ground glass opacity (GGO), consolidation, crazy paving pattern, lobes affected and septal thickening between heart failure and COVID-19 pneumonia. However, less rounded morphology (8.3% vs. 67%, p=0.003), more peribronchovascular thickening (75% vs. 33%, p=0.041) and fissural thickening (33% vs. 0%, p=0.028), less peripheral distribution (33% vs. 92%, p=0.003) were found in heart failure group than that in COVID-19 group. Importantly, there were also more patients with upper pulmonary vein enlargement (75% vs. 8.3%, p=0.001), subpleural effusion and cardiac enlargement in heart failure group than that in COVID-19 group (50% vs. 0%, p=0.005, separately). Besides, more fibrous lesions were found in COVID-19 group although there was no statistical difference (25% vs. 0%, P=0.064) CONCLUSIONS Although there are some overlaps of CT imaging between heart failure and COVID-19, CT is still a useful tool in differentiating COVID-19 pneumonia.

negative: Novel coronavirus 2019 (COVID-19): A case report and review of treatments RATIONALE: Novel coronavirus 2019 (COVID-19) also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, non-segmented positive-sense RNA virus belonging to the beta-coronaviridae family. This virus is known to cause severe bilateral pneumonia and acute respiratory distress syndrome (ARDS) which can lead to difficulty breathing requiring mechanical ventilation and intensive care unit management. PATIENT CONCERNS: A 77-year-old female with a history of hypertension and hyperlipidemia who presented as a transfer to our hospital facility with worsening fevers, cough, and respiratory distress. DIAGNOSIS: Chest X-rays revealed bilateral infiltrates worse at the lung bases and CT scan of the chest showed bilateral ground-glass opacities consistent with COVID-19. While our testing revealed a negative COVID-19 result at our institution, the result at a previous hospital returned a positive result. INTERVENTIONS: She was being treated aggressively in the intensive care unit with high dose intravenous ascorbic acid, hydroxychloroquine, and anti-interleukin-6 monoclonal antibody. She also received a loading dose of remdesivir however was unable to complete the course due to organ failure and requirement of vasopressors for hemodynamic stability. OUTCOMES: She remained critically ill and was eventually placed on comfort care as per the family's wishes and passed away. LESSONS: With a rapidly growing death rate and more than 200,000 confirmed cases worldwide, COVID-19 has become a global pandemic and major hit to our healthcare systems. While several companies have already begun vaccine trials and healthcare facilities have been using a wide-range of medications to treat the virus and symptoms, there is not yet an approved medication regimen for COVID-19 infections. The alarming increase in cases per day adds additional pressure to find a cure and decrease the global health burden and mortality rate.

negative: Do we know when to end isolation of persons affected with COVID-19?

negative: Important considerations regarding the future management of Coronavirus (COVID-19)

negative: Author response to Letter to the Editor ‘Liver impairment associated with disease progression in COVID‐19 patients’ We chose the CAP patients hospitalized in our hospital last year as the control because there was no suitable healthy control group available now. And considering the diverse etiology of CAP, the liver impairment appeared in CAP patients maybe result from ischemia/hypoxia-reperfusion injury, systemic inflammatory response or drug use before hospitalization, besides the pathogen itself.

negative: Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: A multicenter cohort study Background: Patients with pre-existing cirrhosis are considered at increased risk of severe coronavirus disease 2019 (COVID-19) but the clinical course in these patients has not yet been reported. This study aimed to provide a detailed report of the clinical characteristics and outcomes among COVID-19 patients with pre-existing cirrhosis. Methods: In this retrospective, multicenter cohort study, we consecutively included all adult inpatients with laboratory-confirmed COVID-19 and pre-existing cirrhosis that had been discharged or had died by 24 March 2020 from 16 designated hospitals in China. Demographic, clinical, laboratory and radiographic findings on admission, treatment, complications during hospitalization and clinical outcomes were collected and compared between survivors and non-survivors. Findings: Twenty-one patients were included in this study, of whom 16 were cured and 5 died in hospital. Seventeen patients had compensated cirrhosis and hepatitis B virus infection was the most common etiology. Lymphocyte and platelet counts were lower, and direct bilirubin levels were higher in patients who died than those who survived (p= 0.040, 0.032, and 0.006, respectively). Acute respiratory distress syndrome and secondary infection were both the most frequently observed complications. Only one patient developed acute on chronic liver failure. Of the 5 non-survivors, all patients developed acute respiratory distress syndrome and 2 patients progressed to multiple organ dysfunction syndrome. Interpretation: Lower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in SARS-CoV-2-infected patients with pre-existing cirrhosis.

negative: Clinical Features and Short-term Outcomes of 102 Patients with Corona Virus Disease 2019 in Wuhan, China OBJECTIVE: In December, 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate clinical and laboratory features and short-term outcomes of patients with Corona Virus Disease 2019(COVID-19). METHODS: All patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between January 3 and February 1, 2020 were included. All those patients were with laboratory-confirmed infection. Epidemiological, clinical, radiological characteristics, underlying diseases, laboratory tests treatment, complications and outcomes data were collected. Outcomes were followed up at discharge until Feb 15, 2020. RESULTS: The study cohort included 102 adult patients. The median (IQR) age was 54 years (37-67years) and 48.0% were female. A total of 34 patients (33.3%) were exposed to source of transmission in the hospital setting (as health care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. Eighteen patients (17.6%) were admitted to the ICU, and 17 patients died (mortality, 16.7%; 95% confidence interval [CI], 9.4%-23.9%). Among patients who survived, they were younger, more likely were health care workers and less likely suffered from comorbidities. They were also less likely suffered from complications. There was no difference in drug treatment rates between the survival and non-survival groups. Patients who survived less likely required admission to the intensive care unit (14.1% vs. 35.3%). Chest imaging examination showed that death patients more likely had ground-glass opacity (41.2% vs. 12.9%). CONCLUSIONS: The mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. Patient characteristics seen more frequently in those who died were development of systemic complications following onset of the illness and the severity of disease requiring admission to the ICU. Our data support those described by others that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatment.

negative: How likely are COVID-19 interventions to benefit the sickest patients?

negative: Comparison of chest CT images between confirmed and suspected cases of COVID-19/ 中华放射学杂志 Objective@#To explore the value of chest CT features and clinical indexes in the differential diagnosis between suspected COVID-19 with two or more negative nucleic acid tests and confirmed COVID-19.@*Methods@#The clinical data and chest CT images of 105 cases withconfirmedCOVID-19 (55 males and 50 females, aged from 2 month to 88 years) and 97 cases with suspected COVID-19(59 males and 38 females, aged from 1 month to 93 years) were analyzed retrospectively in Shiyan Taihe Hospital from January 21 to February 10, 2020. χ2test and two independent sample t test were used to analyze the clinical data and CT signs of the two cases, with P<0.05 for the difference statistically significant.@*Results@#Compared with the suspected patients, the average age of diagnosis of covid-19 was higher (t = 2.460, P = 0.01). The main pathological changes were pure ground glass (68 cases) and mixed ground glass density (53 cases) (χ2 = 50.016, P< 0.01). Interstitial thickening (83 cases) (χ2 = 55.395, P< 0.01), vascular thickening (73 cases) (χ2 = 57.527, P< 0.01), air bronchoscopic sign or bronchiectasis Zhang (67 cases) (χ2 = 17.899, P< 0.01), cord focus (54 cases) (χ2 = 5.500, P = 0.02), easily distributed under the pleura and the long axis of the lesion was parallel to the pleura (89 cases) (χ2 = 23.597, P< 0.01), most of them had no pleural effusion (χ2 = 7.017, P< 0.01); both lesions were mainly distributed in patches (89 cases were confirmed, 87 suspected) (χ2 = 19.573, P< 0.01). In addition, the lesions of patients with confirmed covid-19 showed progress in short term (72 / 87, 82.76%), and those with suspected covid-19 showed remission in short term (63 / 89, 70.78%). The difference was statistically significant (χ2 = 51.114, P< 0.01). There was no significant difference in gender and distribution of pulmonary lobes (χ2 = 1.462, P= 0.23; χ2 = 7.381, P= 0.19). The number of white blood cells (χ2 = 17.891, P< 0.01) and the percentage of lymphocytes (χ2 = 11.151,P< 0.01) of covid-19 were mostly normal or decreased, creatine kinase (χ2 = 9.589, P< 0.01) were mostly normal, and erythrocyte sedimentation rate was mostly normal or increased (χ2 = 4.240, P= 0.04).@*Conclusions@#The imaging features and biochemical indexes of diagnosed COVID-19 are different from those of suspected COVID-19. The comparative analysis of imaging features, clinical indexes and reexamination are helpful for the differential diagnosis of COVID-19 and suspected COVID-19.

negative: Psychological distress found among exposed health care workers Recent research to assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID‐19 in China has found that many are psychologically stressed, raising concerns about the psychological well‐being of physicians and nurses involved in the acute COVID‐19 outbreak.

negative: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19). Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.

negative: CORD-19: The COVID-19 Open Research Dataset The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.

negative: Prognostic value of NT-proBNP in patients with severe COVID-19 BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020,

negative: Predictive Modeling on the Number of Covid-19 Death Toll in the United States Considering the Effects of Coronavirus-Related Changes and Covid-19 Recovered Cases COVID-19 is caused by a coronavirus called SARS-CoV-2. Many countries around the world implemented their own policies and restrictions designed to limit the spread of Covid-19 in recent months. Businesses and schools transitioned into working and learning remotely. In the United States, many states were under strict orders to stay home at least in the month of April. In recent weeks, there are some significant changes related restrictions include social-distancing, reopening states, and staying-at-home orders. The United States surpassed 2 million coronavirus cases on Monday, June 15, 2020 less than five months after the first case was confirmed in the country. The virus has killed at least 115,000 people in the United States as of Monday, June 15, 2020, according to data from Johns Hopkins University. With the recent easing of coronavirus-related restrictions and changes on business and social activity such as stay-at-home, social distancing since late May 2020 hoping to restore economic and business activities, new Covid-19 outbreaks are on the rise in many states across the country. Some researchers expressed concern that the process of easing restrictions and relaxing stay-at-home orders too soon could quickly surge the number of infected Covid-19 cases as well as the death toll in the United States. Some of these increases, however, could be due to more testing sites in the communities while others may be are the results of easing restrictions due to recent reopening and changed policies, though the number of daily death toll does not appear to be going down in recent days due to Covid-19 in the U.S. This raises the challenging question: * How can policy decision-makers and community leaders make the decision to implement public policies and restrictions and keep or lift staying-at-home orders of ongoing Covid-19 pandemic for their communities in a scientific way? In this study, we aim to develop models addressing the effects of recent Covid-19 related changes in the communities such as reopening states, practicing social-distancing, and staying-at-home orders. Our models account for the fact that changes to these policies which can lead to a surge of coronavius cases and deaths, especially in the United States. Specifically, in this paper we develop a novel generalized mathematical model and several explicit models considering the effects of recent reopening states, staying-at-home orders and social-distancing practice of different communities along with a set of selected indicators such as the total number of coronavirus recovered and new cases that can estimate the daily death toll and total number of deaths in the United States related to Covid-19 virus. We compare the modeling results among the developed models based on several existing criteria. The model also can be used to predict the number of death toll in Italy and the United Kingdom (UK). The results show very encouraging predictability for the proposed models in this study. The model predicts that 128,500 to 140,100 people in the United States will have died of Covid-19 by July 4, 2020. The model also predicts that between 137,900 and 154,000 people will have died of Covid-19 by July 31, and 148,500 to 169,700 will have died by the end of August 2020, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the Covid-19 death data available on June 13, 2020. The model also predicts that 34,900 to 37,200 people in Italy will have died of Covid-19 by July 4, and 36,900 to 40,400 people will have died by the end of August based on the data available on June 13, 2020. The model also predicts that between 43,500 and 46,700 people in the United Kingdom will have died of Covid-19 by July 4, and 48,700 to 51,900 people will have died by the end of August, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the data available on June 13, 2020. The model can serve as a framework to help policy makers a scientific approach in quantifying decision-makings related to Covid-19 affairs.

negative: Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID‐19: initial assessment INTRODUCTION: Several antiretroviral drugs are being considered for the treatment of COVID‐19, the disease caused by a newly identified coronavirus, (SARS‐CoV‐2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials. METHODS: Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID‐19 treated with antiretrovirals. RESULTS: From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID‐19. In one randomized trial 99 patients with severe COVID‐19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post‐exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size. CONCLUSIONS: On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID‐19.

negative: Informational needs assessment of non‐Hodgkin lymphoma survivors and their physicians

negative: A prospective, randomized controlled trial of single-incision laparoscopic vs conventional 3-port laparoscopic appendectomy for treatment of acute appendicitis. BACKGROUND Proponents of single-incision laparoscopic surgery (SILS) claim patients have less pain, faster recovery, and better long-term cosmetic results than patients who undergo multiport laparoscopy. However, randomized comparisons are lacking. This study presents the results of a prospective randomized trial of SILS or 3-port laparoscopic appendectomy. STUDY DESIGN Adults with uncomplicated acute appendicitis were randomized 1:1 to either SILS or 3-port laparoscopic appendectomy. The primary end point was early postoperative pain (measured by opiate usage and pain score in the first 12 hours). Secondary end points were operative time, complication rate (including conversions), and recovery time (days of oral opiate usage and return to work). After 6 months, body image and cosmetic appearance were assessed using a validated survey. RESULTS The trial was planned for 150 patients, but was halted after 75 patients when planned interim analysis showed that SILS patients had more postoperative pain (pain score: 4.4 ± 1.6 vs 3.5 ± 1.5; p = 0.01) and higher inpatient opiate usage (hydromorphone use: 3.9 ± 1.9 mg vs 2.8 ± 1.7 mg; p = 0.01) than 3-port laparoscopy. Operative time for SILS averaged 40% longer (54 ± 17 minutes vs 38 ± 11 minutes; p < 0.01). Only 1 SILS case was converted to 3-port. There were no significant differences in length of stay, complications, oral pain medication usage after discharge, or return to work. After 6 months, body image and cosmetic appearance were excellent for both groups and indistinguishable by most measures. However, 3-port patients reported better physical attractiveness (4.0 ± 0.4 vs 3.8 ± 0.4; p = 0.04) and SILS patients reported better scars (score 18.4 ± 2.7 vs 16.4 ± 3.0; p < 0.01). Results are reported as mean ± SD. CONCLUSIONS Single-incision laparoscopic surgery appendectomy resulted in more pain and longer operative times without improving short-term recovery or complications. Long-term body image and cosmetic appearance were excellent in both groups.

negative: Association between Initial Chest CT or Clinical Features and Clinical Course in Patients with Coronavirus Disease 2019 Pneumonia OBJECTIVE: To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values < 1 indicated a lower rate of discharge at four weeks and longer time until discharge. RESULTS: Thirty-two patients recovered and were discharged during the study period with a median length of admission of 16 days (range, 9 to 25 days), while the rest remained hospitalized at the end of this study (median, 17.5 days; range, 4 to 27 days). None died during the study period. After controlling for age, onset time, lesion characteristics, number of lung lobes affected, and bilateral involvement, the lung severity score on baseline CT (> 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18–0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03–0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. CONCLUSION: Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.

negative: Outbreak dynamics of COVID-19 in China and the United States On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in [Formula: see text] provinces, we found a latent period of 2.56 ± 0.72 days, a contact period of 1.47 ± 0.32 days, and an infectious period of 17.82 ± 2.95 days. We postulate that the latent and infectious periods are disease-specific, whereas the contact period is behavior-specific and can vary between different provinces, states, or countries. For the early stages of the outbreak in the United States, in [Formula: see text] states, we adopted the disease-specific values from China and found a contact period of 3.38 ± 0.69 days. Our network model predicts that—without the massive political mitigation strategies that are in place today—the United States would have faced a basic reproduction number of 5.30 ± 0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lockdown, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.

negative: Methods for forecasting the effect of exogenous risk on stock markets Markets are subjected to both endogenous and exogenous risks that have caused disruptions to financial and economic markets around the globe, leading eventually to fast stock market declines. In the past, markets have recovered after any economic disruption. On this basis, we focus on the outbreak of COVID-19 as a case study of an exogenous risk and analyze its impact on the Standard and Poor's 500 (S\&P500) index. We assumed that the S\&P500 index reaches a minimum before rising again in the not-too-distant future. Here we present two cases to forecast the S\&P500 index. The first case uses an estimation of expected deaths released on 02/04/2020 by the University of Washington. For the second case, it is assumed that the peak number of deaths will occur 2-months since the first confirmed case occurred in the USA. The decline and recovery in the index were estimated for the following three months after the initial point of the predicted trend. The forecast is a projection of a prediction with stochastic fluctuations described by $q$-gaussian diffusion process with three spatio-temporal regimes. Our forecast was made on the premise that any market response can be decomposed into an overall deterministic trend and a stochastic term. The prediction was based on the deterministic part and for this case study is approximated by the extrapolation of the S\&P500 data trend in the initial stages of the outbreak. The stochastic fluctuations have the same structure as the one derived from the past 24 years. A reasonable forecast was achieved with 85\% of accuracy.

negative: Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.

negative: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2–14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3–4 days without truncation and at 5–9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.

negative: Practice considerations on the use of investigational anti‐COVID‐19 medications: Dosage, administration and monitoring WHAT IS KNOWN AND OBJECTIVE: Understanding investigational medications is important. Many older drugs are being investigated for repurposing against COVID‐19. We comment on various drugs currently undergoing such trials to optimize their safe use. COMMENT: We describe medications used during early COVID‐19 outbreaks in South Korea, focusing on practice aspects including the method of drug administration, drug formulation, patient‐monitoring for adverse reactions and drug interactions informed by our experience during the 2015 outbreak of Middle East respiratory syndrome (MERS). We comment on hydroxychloroquine, chloroquine, lopinavir/ritonavir with zinc supplement, remdesivir, tocilizumab, ciclesonide, niclosamide and high‐dose intravenous immunoglobulin (IVIG). WHAT IS NEW AND CONCLUSION: Effective therapies are urgently needed to manage COVID‐19, and existing drugs such as antivirals and antimalarials are under investigation for repurposing to meet this need. This process requires up‐to‐date drug information to ensure optimum use, particularly safety and efficacy profiles of the medications, until convincing evidence is reported.

negative: Practical considerations for the diagnosis and treatment of fibrotic interstitial lung disease during the COVID-19 pandemic Abstract The 2019 coronavirus disease (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected virtually all aspects of patient care. Healthcare systems around the world are trying to simultaneously treat patients with COVID-19 infection, prepare for its long-term impacts, and manage patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks.

negative: Resilience of local food systems and links to food security – A review of some important concepts in the context of COVID-19 and other shocks The objective of this review is to explore and discuss the concept of local food system resilience in light of the disruptions brought to those systems by the 2020 COVID-19 pandemic. The discussion, which focuses on low and middle income countries, considers also the other shocks and stressors that generally affect local food systems and their actors in those countries (weather-related, economic, political or social disturbances). The review of existing (mainly grey or media-based) accounts on COVID-19 suggests that, with the exception of those who lost members of their family to the virus, as per June 2020 the main impact of the pandemic derives mainly from the lockdown and mobility restrictions imposed by national/local governments, and the consequence that the subsequent loss of income and purchasing power has on people’s food security, in particular the poor. The paper then uses the most prominent advances made recently in the literature on household resilience in the context of food security and humanitarian crises to identify a series of lessons that can be used to improve our understanding of food system resilience and its link to food security in the context of the COVID-19 crisis and other shocks. Those lessons include principles about the measurement of food system resilience and suggestions about the types of interventions that could potentially strengthen the abilities of actors (including policy makers) to respond more appropriately to adverse events affecting food systems in the future.

negative: The role of ECMO in COVID‐19: Can it provide rescue therapy in those who are critically ill? Arising from the city of Wuhan, Hubei province in China, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 has been rapidly spreading since its first presentation in late 2019. The World Health Organization declared a pandemic on the 11th March 2020, and as of 29th of April 2020 more than 3 million cases have been reported worldwide with over 225 000 confirmed deaths. Where mechanical ventilation may not be enough, extracorporeal membrane oxygenation (ECMO) could play a role as a form of rescue therapy and may provide beneficial results in the hands of skilled clinicians in centers with experience of using ECMO appropriately in selected patients. Our understanding of COVID‐19 is ever‐changing and the need for intensive care beds is rising, which means that ECMO will surely play a key role in the near future.

negative: Practice of Pharmaceutical Care in Designated Hospital under the Condition of Novel Coronavirus Pneumonia Epidemic/ 中国药房 OBJECTIVE：To shar e the experienc e of pharmaceutical care in Wuhan Jinyintan Hospital （herein after refers to “our hospital ”）under the condition of novel coronavirus pneumonia （COVID-19）epidemic，and to provide reference for other hospitals to deal with public health emergencies. METHODS ：The situation of pharmaceutical care in our hospital under the condition of COVID- 19 epidemic was summarized and shared ，including the epidemic prevention and control management （regional division ，disinfection management ，pharmacy personnel training ），supply of drugs and disinfection products ，the monitoring and education of rational drug use by information technology. RESULTS ：The pharmacy department of our hospital divided the activity scope into clean area ，potential pollution risk area ，semi pollution area ，and implement different disinfection management. All pharmacists received training ，involving personal health protection ，prevention and control knowledge of COVID-19，health status monitoring ，etc. For supply and guarantee of drugs and disinfectants ，the epidemic drug list of our hospital was formulated ，drugs and disinfectants were purchased accurately and stored in a standardized way. 24 h response telephone was set up in the clinical pharmacy room to receive consultation from clinicians on drug use at any time. The drugs mentioned in the COVID- 19 diagnosis scheme were compared in terms of the mechanism of action and the medication of special populations to form a tablet ，so as to help clinical rational choice treatment drug. CONCLUSIONS ：The pharmaceutical care in the designated hospital of COVID- 19 is a professional and complicated work ，involving a wide range of aspects. Pharmacy department must respond actively and adjust the strategy in time so as to play an important role in improving the ability of medical treatment.

negative: International Electronic Health Record-Derived COVID-19 Clinical Course Profiles: The 4CE Consortium We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across 5 countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on comorbidities and temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.

negative: Current status of potential therapeutic candidates for the COVID-19 crisis Abstract As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.

negative: Effect of Health Education on Healthcare-Seeking Behavior of Migrant Workers in China Health education is considered to be an effective way to improve the healthcare-seeking behavior of migrant workers. This study examined the impact of health education on healthcare-seeking behavior of migrant workers in China and explored the differences in different health education methods. This paper used the 2017 China Migrants Dynamic Survey (CMDS) to analyze the relationship between health education and healthcare-seeking behavior. Our results indicated that health education could significantly improve the healthcare-seeking behavior of migrant workers, but there was still ample space for improvement. From the perspective of different health education methods, lectures, public consultation, and online education were positively correlated to healthcare-seeking behavior, while publicity materials and bulletin boards were not. Although the effects of publicity materials and bulletins were limited, these two health education methods were still the most widely used. Our results emphasized the necessity of increasing investment in lectures, public consultation, online education, and other similar health education methods. This change in health education methods can play an effective role in the spread of health education to improve the healthcare-seeking behavior of migrant workers.

negative: Pulmonary fibrosis secondary to COVID-19: a call to arms?

negative: Predicting COVID-19 malignant progression with AI techniques Background: The coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since mid-December 2019, which greatly challenge public medical systems. With limited medical resources, it is a natural strategy, while adopted, to access the severity of patients then determine the treatment priority. However, our work observes the fact that the condition of many mild outpatients quickly worsens in a short time, i.e. deteriorate into severe/critical cases. Hence, it has been crucial to early identify those cases and give timely treatment for optimizing treatment strategy and reducing mortality. This study aims to establish an AI model to predict mild patients with potential malignant progression. Methods: A total of 133 consecutively mild COVID-19 patients at admission who was hospitalized in Wuhan Pulmonary Hospital from January 3 to February 13, 2020, were selected in this retrospective IRB-approved study. All mild patients at admission were categorized into groups with or without malignant progression. The clinical and laboratory data at admission, the first CT, and the follow-up CT at severe/critical stage of the two groups were compared with Chi-square test, Fisher's exact test, and t test. Both traditional logistic regression and deep learning-based methods were used to build the prediction models. The area under ROC curve (AUC) was used to evaluate the models. Results: The deep learning-based method significantly outperformed logistic regression (AUC 0.954 vs. 0.893). The deep learning-based method achieved a prediction AUC of 0.938 by combining the clinical data and the CT data, significantly outperforming its counterpart trained with clinical data only by 0.141. By further considering the temporal information of the CT sequence, our model achieved the best AUC of 0.954. The proposed model can be effectively used for finding out the mild patients who are easy to deteriorate into severe/critical cases, so that such patients get timely treatments while alleviating the limitations of medical resources.

negative: Coping with Mental Health Challenges During COVID-19 The ongoing pandemic of COVID-19 is a global challenge which resulted in significant morbidity and mortality worldwide. It has also adversely affected the economy and social integrity. There is rising concern about the mental health challenges of the general population, COVID-19-infected patients, close contacts, elderly, children and health professionals. This chapter focusses on various mental health challenges during the COVID-19 pandemic.

negative: The time scale of asymptomatic transmission affects estimates of epidemic potential in the COVID-19 outbreak The role of asymptomatic carriers in transmission poses challenges for control of the COVID-19 pandemic. Study of asymptomatic transmission and implications for surveillance and disease burden are ongoing, but there has been little study of the implications of asymptomatic transmission on dynamics of disease. We use a mathematical framework to evaluate expected effects of asymptomatic transmission on the basic reproduction number [Formula: see text] (i.e., the expected number of secondary cases generated by an average primary case in a fully susceptible population) and the fraction of new secondary cases attributable to asymptomatic individuals. If the generation-interval distribution of asymptomatic transmission differs from that of symptomatic transmission, then estimates of the basic reproduction number which do not explicitly account for asymptomatic cases may be systematically biased. Specifically, if asymptomatic cases have a shorter generation interval than symptomatic cases, [Formula: see text] will be over-estimated, and if they have a longer generation interval, [Formula: see text] will be under-estimated. Estimates of the realized proportion of asymptomatic transmission during the exponential phase also depend on asymptomatic generation intervals. Our analysis shows that understanding the temporal course of asymptomatic transmission can be important for assessing the importance of this route of transmission, and for disease dynamics. This provides an additional motivation for investigating both the importance and relative duration of asymptomatic transmission.

negative: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5–29·1) of the health-care workforce needing to provide care for children aged 3–12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8–15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.

negative: Predictors of help-seeking duration in adult-onset psychosis in Hong Kong. PURPOSE Delay in receiving treatment in psychosis may lead to adverse consequences. We examined the predictors for help-seeking duration in adult-onset psychosis Chinese patients in Hong Kong. We hypothesized that factors which are more related to the illness manifestation would be predictive of waiting time before any help-seeking initiation, and factors which are more related to one's knowledge about mental health services would be predictive of help-seeking duration. METHODS First-episode patients with psychosis were recruited from the Jockey Club Early Psychosis project. They were asked to report retrospectively all help-seeking behaviors involved since their first occurrence of psychotic symptoms until receipt of effective psychiatric treatment. Baseline characteristics, pre-morbid functioning and traits, and mode of illness onset were assessed. RESULTS Help-seeking pattern was analyzed in 360 patients who had subsequently reached the psychiatric services. They had an average of 2.5 help-seeking contacts. Nearly half of the first help-seeking process was initiated by family members. Only 1 % approached priests or traditional healers as the first step in help-seeking. Whereas a gradual mode of onset was significantly associated with longer waiting time to first help-seeking initiation, more premorbid schizoid and schizotypal traits and a migrant status were related to longer help-seeking duration. CONCLUSIONS Current findings suggested that family members were the key decision makers in initiating help-seeking. Longer help-seeking duration in migrants has significant implications to both local and global mental health policy.

negative: Weather Conditions and COVID-19 Transmission: Estimates and Projections Background: Understanding and projecting the spread of COVID-19 requires reliable estimates of how weather components are associated with the transmission of the virus. Prior research on this topic has been inconclusive. Identifying key challenges to reliable estimation of weather impact on transmission we study this question using one of the largest assembled databases of COVID-19 infections and weather. Methods: We assemble a dataset that includes virus transmission and weather data across 3,739 locations from December 12, 2019 to April 22, 2020. Using simulation, we identify key challenges to reliable estimation of weather impacts on transmission, design a statistical method to overcome these challenges, and validate it in a blinded simulation study. Using this method and controlling for location-specific response trends we estimate how different weather variables are associated with the reproduction number for COVID-19. We then use the estimates to project the relative weather-related risk of COVID-19 transmission across the world and in large cities. Results: We show that the delay between exposure and detection of infection complicates the estimation of weather impact on COVID-19 transmission, potentially explaining significant variability in results to-date. Correcting for that distributed delay and offering conservative estimates, we find a negative relationship between temperatures above 25 degrees Celsius and estimated reproduction number ([R]), with each degree Celsius associated with a 3.1% (95% CI, 1.5% to 4.8%) reduction in [R]. Higher levels of relative humidity strengthen the negative effect of temperature above 25 degrees. Moreover, one millibar of additional pressure increases [R] by approximately 0.8 percent (95% CI, 0.6% to 1%) at the median pressure (1016 millibars) in our sample. We also find significant positive effects for wind speed, precipitation, and diurnal temperature on [R]. Sensitivity analysis and simulations show that results are robust to multiple assumptions. Despite conservative estimates, weather effects are associated with a 43% change in [R] between the 5th and 95th percentile of weather conditions in our sample. Conclusions: These results provide evidence for the relationship between several weather variables and the spread of COVID-19. However, the (conservatively) estimated relationships are not strong enough to seasonally control the epidemic in most locations.

negative: An Epidemiological Study on COVID-19: A Rapidly Spreading Disease Background The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a major public health crisis worldwide and challenged healthcare systems across the six continents. The high infectivity of the disease led many governments to adopt strict regulations and measures with the aim of containing its spread. The purpose of this study is to assess the incidence, severity, and territorial expansion of COVID-19. Methods Data from the World Health Organization was screened, and COVID-19 situation reports were extracted from January 21 up till March 14 (inclusive). Our data included the total number of cases, total number of new cases, total number of cured cases, and total number of related deaths. Percentage change of cases over the days of our study were calculated using the Joinpoint regression, with a significance level set at greater than 0.05. Results The total number of COVID-19 cases reached 156,622, with 5,845 subsequent deaths. China, Italy, and Iran have the highest number of cases worldwide. During the first 22 days, the incidence rate of COVID-19 increased significantly to reach 1.81 cases per million persons (p<0.001). That was followed by a significant decrease over the next 11 days (p<0.001) to reach 0.071 cases per million persons. A steady rise then followed, which saw a significant increase in incidence rate to 1.429 cases per million persons (p<0.001). Percentages of death and cured cases varied across the different countries; nevertheless, death percentages have generally been decreasing since the start of the crisis. Conclusion Adopting precautionary regulations such as social isolation, increasing sanitation, and employing strict quarantine measures have proved to be beneficial in containing the virus. Further research needs to be conducted to help discover therapeutic modalities and improve outcomes.

negative: Ongoing Clinical Trials for the Management of the COVID-19 Pandemic COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response.

negative: Dysosmia and dysgeusia due to the 2019 Novel Coronavirus; a hypothesis that needs further investigation

negative: Mental health groups providing support, education in wake of COVID‐19 As news and updates continue to spread regarding the new coronavirus (COVID‐19), the deadly virus that causes respiratory illness and pneumonia, mental health groups and organizations have issued information to consumers, providers and the mental health community at large about ways of addressing the virus and seeking information from public health sources.

negative: COVID-19 AND PATIENTS UNDERGOING PHARMACOLOGICAL TREATMENTS FOR IMMUNE-MEDIATED INFLAMMATORY DISEASES: PROTOCOL FOR A RAPID LIVING SYSTEMATIC REVIEW CONTEXT AND OBJECTIVE: We propose to systematically review the available evidence to evaluate if patients with immune mediated inflammatory diseases under pharmacological treatment with immunosuppressants, immunobiologics, Disease-Modifying Anti-Rheumatic Drugs (DMARD) or targeted synthetic DMARDs have better or worse outcomes when infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study is a protocol for our rapid living systematic review. METHODS: Protocol for a rapid living systematic review methodology following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidance. To conduct the rapid systematic review, we will employ abbreviated systematic review methods, including: not performing independent screens of abstracts and not searching grey literature. As this will be a living review, it will be continuously updated.

negative: COVID-19 containment policies through time may cost more lives at metapopulation level The rapid and pandemic spread of COVID-19 has led to unprecedented containment policies in response to overloaded health care systems. Disease mitigation strategies require informed decision-making to ensure a balance between the protection of the vulnerable from disease and the maintenance of global economies. We show that temporally restricted containment efforts, that have the potential to flatten epidemic curves, can result in wider disease spread and larger epidemic sizes in metapopulations. Longer-term rewiring of metapopulation networks or the enforcement of feasible long-term measures that decrease disease transmissions appear to be more efficient than temporarily restricted intensive mitigation strategies (e.g. short-term mass quarantine). Our results may inform balanced containment strategies for short-term disease spread mitigation in response to overloaded health care systems and longer-term epidemiological sizes.

negative: Rehabilitation management of patients with COVID-19. Lessons learned from the first experiences in China Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.

negative: Epidemiological parameters of coronavirus disease 2019: a pooled analysis of publicly reported individual data of 1155 cases from seven countries Background The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between exposure of infector and infectee), serial interval, time point of exposure and basic reproduction number (R0) of COVID-19. Methods Between late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented. Findings In total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and -0.19 day (i.e., 0.19 day before symptom onset of infector) and 3.32 days for time point of exposure. R0 was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before the symptom onsets of infectors. In 27 (3.92%) infector-infectee pairs, symptom onsets of infectees occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed. Interpretation This study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures.

negative: Abstracts from the 37th Annual Meeting of the Society of General Internal Medicine

negative: Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test Background It has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive. Methods A total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods. Findings Up to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP. Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19. Interpretation Our results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients during follow-up. Our findings provide empirical information and evidence for the effective management of COVID-19 patients during their convalescent phase.

negative: COVID19 and Airbnb – Disrupting the disruptor

negative: Respiratory and pulmonary complications in head and neck cancer patients: Evidence-based review for the COVID-19 era BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID-19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID-19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long-term management and health of these patients.

negative: A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: A case report Abstract Introduction An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings. Case A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24. Conclusions Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.

negative: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma of six donors who have recovered from COVID-19 Background: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. Results: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. Conclusions: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. Methods: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.

negative: Deep Sentiment Classification and Topic Discovery on Novel Coronavirus or COVID-19 Online Discussions: NLP Using LSTM Recurrent Neural Network Approach Internet forums and public social media, such as online healthcare forums, provide a convenient channel for users (people/patients) concerned about health issues to discuss and share information with each other. In late December 2019, an outbreak of a novel coronavirus (infection from which results in the disease named COVID-19) was reported, and, due to the rapid spread of the virus in other parts of the world, the World Health Organization declared a state of emergency. In this paper, we used automated extraction of COVID-19–related discussions from social media and a natural language process (NLP) method based on topic modeling to uncover various issues related to COVID-19 from public opinions. Moreover, we also investigate how to use LSTM recurrent neural network for sentiment classification of COVID-19 comments. Our findings shed light on the importance of using public opinions and suitable computational techniques to understand issues surrounding COVID-19 and to guide related decision-making.

negative: Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ? The outbreak of 2019-nCoV pneumonia (COVID-19) in the city of Wuhan, China has resulted in more than 70,000 laboratory confirmed cases, and recent studies showed that 2019-nCoV (SARS-CoV-2) could be of bat origin but involve other potential intermediate hosts. In this study, we assembled the genomes of coronaviruses identified in sick pangolins. The molecular and phylogenetic analyses showed that pangolin Coronaviruses (pangolin-CoV) are genetically related to both the 2019-nCoV and bat Coronaviruses but do not support the 2019-nCoV arose directly from the pangolin-CoV. Our study also suggested that pangolin be natural host of Betacoronavirus, with a potential to infect humans. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks of coronaviruses from wild animals to humans.

negative: Solvable delay model for epidemic spreading: the case of Covid-19 in Italy We present a simple but realistic model for describing the diffusion of an infectious disease on a population of individuals. The dynamics is governed by a single functional delay differential equation, which, in the case of a large population, can be solved exactly, even in the presence of a time-dependent infection rate. This delay model has a higher degree of accuracy than that of the so-called SIR model, commonly used in epidemiology, which, instead, is formulated in terms of a set of three ordinary differential equations. We apply our model to describe the outbreak of the new virus COVID-19 in Italy, taking into account the containment measures implemented by the government in order to mitigate the spreading of the virus and the social costs for the population.

negative: Quantifying Projected Impact of Social Distancing Policies on COVID-19 Outcomes in the US Current social distancing measures to impede COVID-19 (such as shelter-in-place) are economically unsustainable in the long term. Models are needed to understand the implications of possible relaxation options for these measures. We report such models, together with corresponding parameter estimation techniques and prediction outcomes, borrowing insights from another domain; namely, information cascades. Our models assume that the containment of the virus into isolated locales is no longer possible. Instead, we explore options that reduce the rate of spread. We predict COVID-19 contagion trends in different geographic regions under a"what if"scenario to understand the effects of potential policy decisions on regional trends. Our model allows experimentation with other policies that, we hope, can contribute to socially viable outcomes both in terms of health system capacity and economic impact. We apply our model to over 30 highly impacted states in the US and publish the results at https://covid19predictions.csl.illinois.edu/

negative: Neurobiology of COVID-19. Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19, who may present with acute neurological symptoms (e.g., stroke), even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic "NeuroCovid" classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the long-term sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson's disease, or Alzheimer's disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system.

negative: Understanding the T cell immune response in SARS coronavirus infection The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.

negative: The Need of Research Initiatives Amidst and After the Covid-19 Pandemic: A Message from the Editors of the European Journal of Vascular and Endovascular Surgery

negative: Hindsight is 2020 vision: Characterisation of the global response to the COVID-19 pandemic Since the initial outbreak in Wuhan (Hubei, China) in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has rapidly spread to cause one of the most pressing challenges facing our world today: the COVID-19 pandemic. Within four months of the first reported cases, more than two and a half million cases were confirmed with over two hundred thousand deaths globally, and many countries had taken extreme measures to stop the spread. In this work, we analyse the response to the COVID-19 outbreak for 103 countries over the period 22 January to 13 April 2020. We utilise a novel stochastic epidemiological model that includes a regulatory mechanism that captures the level of tolerance to rising confirmed cases within the response behaviour. Using approximate Bayesian computation, we identify that the top ten outbreaks as of 31 March are characterised by a high tolerance to rising cases tallies, whereas countries that avoided severe outbreak have a low tolerance. Countries that recovered rapidly also have a higher identification rate. As of 13 April, almost all countries show declines in transmission rates and basic reproductive numbers. Furthermore, countries approaching recovery also increased their identification rate between 31 March and 13 April. We also demonstrate that uncertainty in undocumented infections dramatically impacts uncertainty in predictions. Overall, we recommend that broader testing is required to understand the magnitude of undocumented infections.

negative: Fire, disease and fear: Effects of the media coverage of 2019-2020 Australian bushfires and novel coronavirus 2019 on population mental health

negative: Evaluation of Glass Wool Filters and Hollow-Fiber Ultrafiltration Concentration Methods for qPCR Detection of Human Adenoviruses and Polyomaviruses in River Water Pathogenic human viruses cause over half of gastroenteritis cases associated with recreational water use worldwide. They are difficult to concentrate from environmental waters due to low numbers and small sizes. Rapid enumeration of viruses by quantitative polymerase chain reaction (qPCR) has the potential to improve water quality analysis and risk assessment. However, capturing and recovering these viruses from environmental water remain formidable barriers to routine use. Here, we compared the recovery efficiencies of human adenoviruses (HAdVs) and human polyomaviruses (HPyVs) from 10-L river water samples seeded with raw human wastewater (100 and 10 mL) using hollow-fiber ultrafiltration (HFUF) and glass wool filter (GWF) methods. The mean recovery efficiencies of HAdVs in river water samples through HFUF were 36 and 86 % for 100 and 10 mL of seeded human wastewater, respectively. In contrast, the estimated mean recovery efficiencies of HAdVs in river water samples through GWF were 1.3 and 3 % for 100 and 10 mL seeded raw human wastewater, respectively. Similar trends were also observed for HPyVs. Recovery efficiencies of HFUF method were significantly higher (P < 0.05) than GWF for both HAdVs and HPyVs. Our results clearly suggest that HFUF would be a preferred method for concentrating HAdVs and HPyVs from river water followed by subsequent detection and quantification with PCR/qPCR assays.

negative: Will novel virus go pandemic or be contained?

negative: Risk-adapted Treatment Strategy For COVID-19 Patients BACKGROUND: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease (COVID-19). The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19. METHODS: We collected the medical records of 55 COVID-19 patients for analysis. We divided these patients into mild, moderate and severe groups, and risk-adapted treatment approaches were given according to the illness severity. RESULTS: Twelve patients were in mild group and 22 were in moderate group (non-severe group, n=34), and 21 patients were in severe group. At the end of the first two weeks after admission, clinical manifestations had completely despeared in 31(91.2%)patients in non-severe group, and 18(85.7%) patients in severe group (p=0.85). Both groups had a satisfied chest CT imaging recovery, which includes 22(64.7%) patients in non-severe group and 12(57.1%) patients in severe group recovered at least 50% of the whole leisions in the first week, and 28(82.4%) and 16(76.2%) recovered at least 75% in the second week, respectively. There were no significant differences in SARS-CoV-2 nucleic acid negativity (p=0.92). There were also no significant differences in the levels of SARS-CoV-2-IgM and IgG antibody production between the two groups (p=0.13, 0.62). There were 45 cases were discharged from the hospital, and no patients died at the time of this clinical analysis. CONCLUSIONS: Risk-adapted treatment strategy was associated with significant clinical manifestations alleviation and clinical imaging recovery. In severe COVID-19 patients, early and short-term use of low-dose methylprednisolone was beneficial and did not delay SARS-CoV-2 nucleic acid clearance and influence IgG antibody production.

negative: Cardiovascular system and COVID-19: perspectives from a developing country. A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the "heart and virus" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.

negative: Effectiveness and safety of available treatments for COVID-19 during pregnancy: a critical review Background: COVID-19 is a pandemic disease caused by the SARS-CoV-2 and it spread globally in the last few months. The complete lack of specific treatment forced clinicians to use old drugs, chosen for their efficacy against similar viruses or their in vitro activity. Trials on patients are ongoing but the majority of information comes from small case series and single center reports. We aimed to provide a literature review on the putative effectiveness and safety of available treatments for COVID-19 in pregnant women. Methods: We reviewed all the available literature concerning the drugs that have been used in the treatment of COVID-19 during pregnancy and whose safe assumption during pregnancy had been demonstrated by clinical studies (i.e. including studies on other infectious diseases). Drugs contra-indicated during pregnancy or with unknown adverse effects were not included in our review. Results and conclusions: Clinical trials are not often conducted among pregnant patients for safety reasons and this means that drugs that may be effective in general population cannot be used for pregnant women due to the lack of knowledge of side effects in this category of people .The choice to use a specific drug for COVID-19 in pregnancy should take into account benefits and possible adverse events in each single case. In the current situation of uncertainty and poor knowledge about the management of COVID-19 during pregnancy, this present overview may provide useful information for physicians with practical implications.

negative: The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis Abstract Objectives An outbreak of novel coronavirus in 2019 threatens the health of people, and there is no proven pharmacological treatment. Although corticosteroids were widely used during outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, their efficacy remainedhighly controversial. We aimed to further evaluate the influence of corticosteroids on patients with coronavirus infection. Methods We conducted a comprehensive search of literature published in PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) from January 1, 2002 to March 15, 2020. All statistical analyses in this study were performed on stata14.0. Results A total of 5270 patients from 15 studies were included in this meta-analysis. The result indicated that critical patients were more likely to require corticosteroids therapy (risk ratio [RR] = 1.56, 95% confidence interval [CI] = 1.28-1.90, P<0.001). However, corticosteroid treatment was associated with higher mortality (RR = 2.11, 95%CI = 1.13-3.94, P = 0.019), longer length of stay (weighted mean difference [WMD] = 6.31, 95%CI = 5.26–7.37, P<0.001), a higher rate of bacterial infection (RR = 2.08, 95%CI = 1.54–2.81, P<0.001), and hypokalemia (RR = 2.21, 95%CI = 1.07–4.55, P = 0.032) but not hyperglycemia (RR = 1.37, 95%CI=0.68–2.76, P = 0.376) or hypocalcemia (RR = 1.35, 95%CI = 0.77–2.37, P = 0.302). Conclusions Patients with severe conditions are more likely to require corticosteroids. Corticosteroid use is associated with increased mortality in patients with coronavirus pneumonia.

negative: Immunology of COVID-19: current state of the science Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

negative: Emerging Infectious Diseases and Antimicrobial Resistance (EIDAR) INTRODUCTION: The Infectious Disease Clinical Research Program’s (IDCRP) Emerging Infectious Diseases and Antimicrobial Resistance (EIDAR) Research Area is a Department of Defense (DoD) clinical research capability that is responsive and adaptive to emerging infectious disease (EID) threats to US military readiness. Among active-duty and other Military Health System (MHS) beneficiaries, EIDAR research is largely focused on evaluating the incidence, risk factors, and acute- and long-term health effects of military-relevant EIDs, especially those caused by high-consequence pathogens or are responsible for outbreaks among US military populations. The EIDAR efforts also address Force Health Protection concerns associated with antimicrobial resistance and antimicrobial stewardship practices within the MHS. METHODS: The EIDAR studies utilize the approach of: (1) Preparing for emergent conditions to systematically collect clinical specimens and data and conduct clinical trials to assist the military with a scientifically appropriate response; and (2) Evaluating burden of emergent military-relevant infectious diseases and assessing risks for exposure and development of post-infectious complications and overall impact on military readiness. RESULTS: In response to the Ebola virus epidemic in West Africa, the IDCRP partnered with the National Institutes of Health in developing a multicenter, randomized safety and efficacy study of investigational therapeutics in Ebola patients. Subsequently, the EIDAR team developed a protocol to serve as a contingency plan (EpICC-EID) to allow clinical research activities to occur during future outbreaks of viral hemorrhagic fever and severe acute respiratory infections among MHS patients. The EIDAR portfolio recently expanded to include studies to understand exposure risks and impact on military readiness for a diversity of EIDs, such as seroincidence of non-Lyme disease borreliosis and Coccidioides fungal infections among high-risk military populations. The team also launched a new prospective study in response to the recent Zika epidemic to conduct surveillance for Zika and other related viruses among MHS beneficiaries in Puerto Rico. Another new study will prospectively follow U.S. Marines via an online health assessment survey to assess long-term health effects following the largest DoD Shiga Toxin-Producing Escherichia coli outbreak at the U.S. Marine Corps Recruit Depot-San Diego. In cooperation with the Trauma-Related Infections Research Area, the EIDAR Research Area is also involved with the Multidrug-Resistant and Virulent Organisms Trauma Infections Initiative, which is a collaborative effort across DoD laboratories to characterize bacterial and fungal isolates infecting combat-related extremity wounds and link lab findings to clinical outcomes. Furthermore, the EIDAR team has developed an Antimicrobial Resistance and Stewardship Collaborative Clinical Research Consortium, comprised of Infectious Disease and Pharmacy specialists. CONCLUSIONS: The EIDAR Research Area is responsive to military-relevant infectious disease threats that are also frequently global public health concerns. Several new EIDAR efforts are underway that will provide Combatant Command Surgeons, Infectious Diseases Service Chiefs, and other Force Health Protection stakeholders with epidemiological information to mitigate the impact of EIDs and antimicrobial resistance on the health of U.S. military service members and their dependents.

negative: Incidence of Adverse Drug Reactions in COVID‐19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System To evaluate the incidence, type, and risk factors associated with adverse drug reactions (ADRs) among patients with coronavirus disease 2019 (COVID‐19) by Hospital Pharmacovigilance System (CHPS). A retrospective analysis was performed on 217 patients with COVID‐19 admitted to the First Hospital of Changsha in China, from January 17, 2020, to February 29, 2020. The active monitoring model in CHPS was used to detect ADR signals of the hospital information system. The risk factors for the ADRs were classified using the World Health Organization‐Uppsala Monitoring Centre (WHO‐UMC) system. Univariate and multivariate logistic regressions were carried out to analyze the risk factors of ADRs. Our results showed that the prevalence of ADRs was 37.8% in the patients, which was predominated by drug‐induced gastrointestinal disorders and liver system disorders (23.0% vs. 13.8%). The ADR could be explained by the use of lopinavir/ ritonavir and umifenovir by 63.8% and 18.1%, respectively. There were 96.8% of ADRs that occurred within 14 days of hospitalization. Multivariable analysis showed that length of stay (odds ratio (OR): 2.02; 95% confidence interval (CI) 1.03–3.96; P = 0.04), number of drugs used in the hospital (OR: 3.17; 95% CI 1.60–6.27; P = 0.001) and underlying basic diseases (OR: 2.07; 95% CI 1.02–4.23; P = 0.04) were independent risk factor for ADRs in the patients. Together, the incidence of ADRs was significantly high during the treatment period. Moreover, the active monitoring of the CHPS system reflected ADRs during COVID‐19 treatment in the real world, which provided reference for safe medication in the clinic.

negative: Epidemiological characteristics of COVID-19: a systematic review and meta-analysis Our understanding of the Coronavirus disease 2019 (COVID-19) continues to evolve and there are many unknowns about its epidemiology. This study aims to synthesise case fatality rate (CFR) among confirmed COVID-19 patients, incubation period and time from onset of COVID-19 symptoms to first medical visit, intensive care unit (ICU) admission, recovery, and death. We searched MEDLINE, Embase, Google Scholar, and bibliographies of relevant articles from 01 December 2019 to 11 March 2020 without any language restrictions. Quantitative studies that recruited people with confirmed COVID-19 diagnosis were included. Two independent reviewers extracted the data. Out of 1675 non-duplicate studies, 43 were included in the meta-analysis. The pooled mean incubation period was 5.68 (99% confidence interval [CI]: 4.78, 6.59) days. The pooled mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.92 (95% CI: 3.95, 5.90), ICU admission was 9.84 (95% CI: 8.78, 10.90), recovery was 18.55 (95% CI: 13.69, 23.41), and death was 15.93 (95% CI: 13.07, 18.79). Pooled CFR among confirmed COVID-19 patients was 0.02 (95% CI: 0.02, 0.03). We found that the incubation period and lag between the onset of symptoms and first clinical visit for COVID-19 are longer than other respiratory viral infections including Middle East respiratory syndrome and severe acute respiratory syndrome; however, the current policy of 14 days of mandatory quarantine for everyone potentially exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be too conservative. Longer quarantine periods might be more justified for extreme cases.

negative: COVID-19 epidemic in Malaysia: Impact of lock-down on infection dynamics COVID-19 epidemic in Malaysia started as a small wave of 22 cases in January 2020 through imported cases. It was followed by a bigger wave mainly from local transmissions resulting in 651 cases. The following wave saw unexpectedly three digit number of daily cases following a mass gathering urged the government to choose a more stringent measure. A limited lock-down approach called Movement Control Order (MCO) was immediately initiated to the whole country as a way to suppress the epidemic trajectory. The lock-down causes a major socio-economic disruption thus the ability to forecast the infection dynamic is urgently required to assist the government on timely decisions. Limited testing capacity and limited epidemiological data complicate the understanding of the future infection dynamic of the COVID-19 epidemic. Three different epidemic forecasting models was used to generate forecasts of COVID-19 cases in Malaysia using daily reported cumulative case data up until 1st April 2020 from the Malaysia Ministry of Health. The forecasts were generated using a Curve Fitting Model with Probability Density Function and Skewness Effect, the SIR Model, and a System Dynamic Model. Method one based on curve fitting with probability density function estimated that the peak will be on 19th April 2020 with an estimation of 5,637 infected persons. Method two based on SIR Model estimated that the peak will be on 20th - 31st May 2020 if Movement Contro (MCO) is in place with an estimation of 630,000 to 800,000 infected persons. Method three based on System Dynamic Model estimated that the peak will be on 17th May 2020 with an estimation of 22,421 infected persons. Forecasts from each of model suggested the epidemic may peak between middle of April to end of May 2020. Keywords: COVID-19, Infection dynamic, Prediction Modeling, SIR, System Learning, Lock-down

negative: Imaging of Coronavirus Disease 2019: A Chinese Expert Consensus Statement Abstract Coronavirus disease 2019 (COVID-19) is highly contagious, mainly causing inflammatory lesions in the lungs, and can also cause damage to the intestine and liver. The rapid spread of the virus that causes coronavirus disease 2019 (COVID-19) pneumonia has posed complex challenges to global public health. Early detection, isolation, diagnosis, and treatment are the most effective means of prevention and control. At present, the epidemic situation of new coronavirus infection has tended to be controlled in China, and it is still in a period of rapid rise in much of the world. The current gold standard for the diagnosis of COVID-19 is the detection of coronavirus nucleic acids, but imaging has an important role in the detection of lung lesions, stratification, evaluation of treatment strategies, and differentiation of mixed infections. This Chinese expert consensus statement summarizes the imaging features of COVID-19 pneumonia and may help radiologists across the world to understand this disease better.

negative: Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

negative: Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: A descriptive study BACKGROUND: With the spread of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, its effect on society is amplified. We aimed to describe the viral detection results across different timepoints throughout the disease course. METHODS: A retrospective study of 301 confirmed COVID-19 patients hospitalized at Tongji Hospital in Wuhan, China, were included. Demographic characteristics of the patients were collected. Upper respiratory specimens (throat and/or nasal swabs) were obtained and analyzed by real-time RT-PCR for SARS-CoV-2 infection. Period of viral infection and the contagious stage were analyzed. RESULTS: Of 301 hospitalized COVID-19 patients, the median age was 58 years and 51.2 % were male. The median period between symptoms presence and positive SARS-CoV-2 RT-PCR results was 16 days (IQR, 10-23, Nâ¯=â¯301). The median period between symptoms presence and an effective negative SARS-CoV-2 RT-PCR result was 20 days (IQR, 17-24; Nâ¯=â¯216). Infected patient ≥65 years old stayed contagious longer (22 days vs 19 days, pâ¯=â¯0.015). Although two consecutive negative results were confirmed in 70 patients, 30 % of them had positive viral test results for the third time. Using specimens from nasal swabs to run the RT-PCR test showed a higher positive rate than using specimens from throat swabs. CONCLUSIONS: This large-scale investigation with 1113 RT-PCR test results from 301 COVID-19 patients showed that the average contagious period of SARS-CoV-2 infected patients was 20 days. Longer observation period and more than 2 series of negative viral test are necessary for patients ≥65 years.

negative: Risk of COVID-19 is associated with long-term exposure to air pollution High risk of severe disease of COVID-19 has been associated with patients with chronic obstructive pulmonary disease, cardiovascular disease or hypertension, and long-term exposure to PM2.5 has been associated with COVID-19 mortality. We collate individual level data of confirmed COVID-19 cases during the first wave of the epidemic in mainland China by March 6, 2020. We pair these data with a mobile phone dataset, covering human movements from Wuhan before the travel ban and inner-city movements during the time of emergency response from 324 cities in China. Adjusting for socio-economic factors, an increase of 10 μg/m3 in NO2 or PM2.5 was found to be associated with a 22.41% (95%CI: 7.28%-39.89%) or 15.35% (95%CI: 5.60%-25.98%) increase in the number of COVID-19 cases, and a 19.20% (95%CI: 4.03%-36.59%) or 9.61% (95%CI: 0.12%-20.01%) increase in severe infection, respectively. Our results highlight the importance of air quality improvements to health benefits.

negative: Systematic rapid "living" review on rehabilitation needs due to covid-19: update to march 31st 2020 BACKGROUND: The outbreak of Covid-19 epidemics has challenged the provision of health care worldwide, highlighting the main flaws of some national health systems with respect to their capacity to cope with the needs of frail subjects. People experiencing disability due to Covid-19 express specific rehabilitation needs that deserve a systematic evidence-based approach. OBJECTIVES: To provide the rehabilitation community with updates on the latest scientific literature on rehabilitation needs due to Covid-19. The first rapid "living" review will present the results of a systematic search performed up to March 31st, 2020. METHODS: A systematic search on PubMed, Pedro and Google Scholar was performed using the search terms: "Covid-19", "Coronavirus", "severe acute respiratory syndrome coronavirus 2", "rehabilitation", "physical therapy modalities", "exercise", "occupational therapy", and "late complications". Papers published up to March 31st, 2020, in English, were included. RESULTS: Out of the 2758 articles retrieved, 9 were included in the present review. Four of them are "calls for action", 3 provide recommendations about rehabilitation interventions in the acute phase, 2 address the needs of people quarantined at home or with restricted mobility due to the lockdown, and 1 provides a Core Outcome Set to be used in clinical trials to test the efficacy of health strategies in managing Covid-19 patients. CONCLUSIONS: All selected papers were based on previous literature and not on the current Covid-19 pandemic. Main messages included: 1) early rehabilitation should be granted to inpatients with Covid-19; 2) people with restricted mobility due to quarantine or lockdown should receive exercise programs to reduce the risk of frailty, sarcopenia, cognitive decline and depression; 3) telerehabilitation may represent the first option for people at home. Further updates are warranted in order to characterize the emerging disability in Covid-19 survivors and the adverse effects on the health of chronically disabled people.

negative: Potential pharmacological agents for COVID-19. A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.

negative: Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status Abstract Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

negative: Heralding Healthcare Professionals: Recognition of Neurological Deficits in COVID-19. The 2019 novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic disease that is dominated by pulmonary symptoms. However, recent reports of isolation of the virus from cerebrospinal fluid (CSF) coupled with radiological evidence of zones of necrosis in the brain, have elucidated the neurotropic potential of SARS-CoV-2. The acute respiratory failure seen in patients with COVID-19 is alarming and could be due to the effects of SARS-CoV-2 on the central respiratory regulatory centers in the brainstem. Appropriate interventions can be implemented to prevent severe outcomes of neurological invasion by SARS-CoV-2 to reduce the morbidity and mortality of patients with COVID-19. It is of paramount importance that the scientific community alerts the healthcare professionals of the pieces of evidence that can herald them on the covert neurological deficits in progress in COVID-19.

negative: Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.

negative: Anticipating and Mitigating the Impact of COVID-19 Pandemic on Alzheimer's Disease and Related Dementias Abstract The COVID-19 pandemic is causing global morbidity and mortality, straining health systems, and disrupting society, putting individuals with Alzheimer's disease and related dementias (ADRD) at risk of significant harm. In this Special Article, we examine the current and expected impact of the pandemic on individuals with ADRD. We discuss and propose mitigation strategies for: the risk of COVID-19 infection and its associated morbidity and mortality for individuals with ADRD; the impact of COVID-19 on the diagnosis and clinical management of ADRD; consequences of societal responses to COVID-19 in different ADRD care settings; the effect of COVID-19 on caregivers and physicians of individuals with ADRD; mental hygiene, trauma, and stigma in the time of COVID-19; and the potential impact of COVID-19 on ADRD research. Amid considerable uncertainty, we may be able to prevent or reduce the harm of the COVID-19 pandemic and its consequences for individuals with ADRD and their caregivers.

negative: Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus A novel Coronavirus pandemic emerged in December of 2019, causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antiviral, strategies for mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of these mitigation strategies. Simulations of the model, using data relevant to COVID-19 transmission in New York state and the entire US, show that the pandemic will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) in New York State and the entire US decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. This study shows that early termination of strict social-distancing could trigger a devastating second wave with burden similar to that projected before the onset of strict social-distance. The use of efficacious face-masks (efficacy greater than 70%) could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of other anti-COVID-19 intervention measures can lead to elimination of the pandemic. The mask coverage needed to eliminate COVID-19 decreases if mask-use is combined with strict social-distancing.

negative: The site of origin of the 1918 influenza pandemic and its public health implications

negative: Society for Cardiovascular Magnetic Resonance (SCMR) guidance for the practice of cardiovascular magnetic resonance during the COVID-19 pandemic The aim of this document is to provide general guidance and specific recommendations on the practice of cardiovascular magnetic resonance (CMR) in the era of the COVID-19 pandemic. There are two major considerations. First, continued urgent and semi-urgent care for the patients who have no known active COVID-19 should be provided in a safe manner for both patients and staff. Second, when necessary, CMR on patients with confirmed or suspected active COVID-19 should focus on the specific clinical question with an emphasis on myocardial function and tissue characterization while optimizing patient and staff safety.

negative: Relationship Between Humans and Their Viruses

negative: Identification of a new human coronavirus Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus was isolated from a 7-month-old child suffering from bronchiolitis and conjunctivitis. The complete genome sequence indicates that this virus is not a recombinant, but rather a new group 1 coronavirus. The in vitro host cell range of HCoV-NL63 is notable because it replicates on tertiary monkey kidney cells and the monkey kidney LLC-MK2 cell line. The viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein. Screening of clinical specimens from individuals suffering from respiratory illness identified seven additional HCoV-NL63-infected individuals, indicating that the virus was widely spread within the human population. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1024) contains supplementary material, which is available to authorized users.

negative: Behavioral Health and Response for COVID-19 Research from financial stress, disasters, pandemics, and other extreme events, suggests that behavioral health will suffer, including anxiety, depression, and posttraumatic stress symptoms. Furthermore, these symptoms are likely to exacerbate alcohol or drug use, especially for those vulnerable to relapse. The nature of coronavirus disease 2019 (COVID-19) and vast reach of the virus, leave many unknows for the repercussions on behavioral health, yet existing research suggests that behavioral health concerns should take a primary role in response to the pandemic. We propose a 4-step services system designed for implementation with a variety of different groups and reserves limited clinical services for the most extreme reactions. While we can expect symptoms to remit overtime, many will also have longer-term or more severe concerns. Behavioral health interventions will likely need to change overtime and different types of interventions should be considered for different target groups, such as for those who recover from COVID-19, health-care professionals, and essential personnel; and the general public either due to loss of loved ones or significant life disruption. The important thing is to have a systematic plan to support behavioral health and to engage citizens in prevention and doing their part in recovery by staying home and protecting others.

negative: Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains. IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.

negative: Vaginal delivery report of a healthy neonate born to a convalescent mother with COVID‐19 The outbreak of the infection of 2019 novel coronavirus disease (COVID‐19) has become a challenging public health threat worldwide. Limited data are available for pregnant women with COVID‐19 pneumonia. We report a case of a convalescing pregnant woman diagnosed with COVID‐19 infection 37 days before delivery in the third trimester. A live birth without severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection was performed successfully via the vagina. The findings from our case indicate that there is no intrauterine transmission in this woman who developed COVID‐19 pneumonia in late pregnancy.

negative: COVID-19 - Where have all the STEMIs gone?

negative: Modelling Recovered Cases and Death Probabilities for the COVID-19 Outbreak From March 23rd, the data for the recovered cases of COVID-19 are missing from the standard repository maintained by the Johns Hopkins University in collaboration with the WHO. But since data concerning recovered patients are extremely important for modelling the COVID-19 outbreak, a method for estimating the missing data is provided and tested. As a byproduct, it produces estimates for the probabilities to die $k$ days after confirmation, or to survive after $d$ days.

negative: Predictors of recovery from post-traumatic stress disorder after the dongting lake flood in China: a 13–14 year follow-up study BACKGROUND: Floods are some of the most common and destructive natural disasters in the world, potentially leading to both physical injuries and psychological disorders, including post-traumatic stress disorder (PTSD). PTSD can damage functional capacity and interfere with social functioning. However, little is known about recovery from PTSD after floods. This study used 2013–2014 follow-up data on survivors of the 1998 Dongting Lake flood who were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD at follow-up and identify predictors of recovery from the PTSD diagnosis in 2000. METHODS: Participants included survivors who had been diagnosed as having PTSD in 2000 after the 1998 Dongting Lake flood. PTSD at follow-up was reassessed using the PTSD Checklist-Civilian version. Information on demographics, trauma-related stressors, post-trauma stressors, social support, and coping style were collected through face-to-face interviews. The association between the independent variables and PTSD at follow-up was analyzed using logistic regression analyses. RESULTS: A total of 201 participants with a PTSD diagnosis in 2000 were included in this study. A total of 19.4 % of the flood survivors with PTSD in 2000 continued to suffer from PTSD in 2013–2014. In the multivariable logistic regression model, individuals who had lost relatives (OR = 12.37, 95 % CI = 2.46–62.16), suffered from bodily injury (OR = 5.01, 95 % CI = 1.92–13.08), had a low level of social support (OR = 5.47, 95 % CI = 1.07–27.80), or had a negative coping style (OR = 4.92, 95 % CI = 1.89–12.81) were less likely to recover from PTSD. CONCLUSIONS: The prevalence rate of PTSD at follow-up indicates that natural disasters such as floods may have a negative influence on survivors’ mental health for an extended period of time. Individuals who have lost relatives, suffered from bodily injury, had a low level of social support, or had a negative coping style were less likely to recover from PTSD. Therefore, effective psychological intervention measures are necessary for facilitating the recovery process from PTSD, especially for individuals with adverse prognostic factors.

negative: Successful recovery of severe COVID-19 with cytokine storm treating with extracorporeal blood purification COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.

negative: What information can I share with my patients about nutrition during COVID-19? In the wake of the current COVID-19 pandemic, nutrition care that focuses on food security is imperative.

negative: Correlation between immune response and self-reported depression during convalescence from COVID-19 Self-reported depression has been observed in coronavirus disease-2019 (COVID-19) patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during discharge from the hospital. However, the cause of this self-reported depression during the convalescent period remains unclear. Here, we report the mental health status of 96 convalescent COVID-19 patients who were surveyed using an online questionnaire at the Shenzhen Samii Medical Center from March 2 to March 12, 2020 in Shenzhen, China. After obtaining their informed consent, we retrospectively analyzed the clinical characteristics of patients, including routine blood and biochemical data. The results suggested that patients with self-reported depression exhibited increased immune response, as indicated by increased white blood cell and neutrophil counts, as well as neutrophil-to-lymphocyte ratio. However, the mechanism linking self-reported depression to these cellular changes needs further study. In conclusion, self-reported depression occurred at an early stage in convalescent COVID-19 patients, and changes in immune function were apparent during short-term follow-up of these patients after discharge. Appropriate psychological interventions are necessary, and changes in immune function should be emphasized during long-term follow up of these patients.

negative: Work-Associated Trauma Traumatic events are experienced by most people at some point in their life. Following a traumatic event many individuals return to previous functioning and some feel an increased sense of efficacy. However, a sizable minority experience adverse psychological and behavioral effects. These effects include distress reactions, health risk behaviors, and psychiatric disorders. Workplace traumatic events and responses most studied in physicians include exposure to injured and dying patients, medical errors and complications, bullying, disasters, and workplace violence. Developmental issues confer specific risks for medical students and residents, as well as early and late career physicians. Prevention measures which reduce exposure to workplace trauma are optimal. Physicians exposed to traumatic events will benefit from the use of prompt, evidence-based interventions. Many will seek and benefit from self-help interventions and peer support, but some may need formal assessment and treatment through employee assistance programs and traditional psychiatric care. Effective prevention and treatment can enhance physician well-being and career retention as well as patient outcomes.

negative: A rate equation approach to model the denaturation or replication behavior of the SARS coronavirus As a newly emerging virus, little is known about the SARS coronavirus, whose outbreak has brought away several hundred people’s lives over the world in the year of 2003 and is seriously imperiling the human health. Revealing the denaturation and replication mechanisms of SARS coronavirus has great importance for successfully fighting SARS. However, experiments related to SARS coronavirus are extremely dangerous and therefore restricted only to certain specific labs with high safety standard. Clearly, predicting the behaviors of SARS coronavirus in a wide variety of environmental conditions, which are not easily accessible, are thus critically necessary. In this study, we proposed to quantify the survival time of SARS coronavirus either in vitro or in vivo, through introducing thermal rate process models established from the well-known Arrhenius law. The complex physical and chemical behaviors of the SARS coronavirus can then be attributed to its activation energy, frequency factor, damage function as well as the surrounding environmental conditions. Based on the first data on stability and resistance of SARS coronavirus measured by members of WHO laboratory network, the rate coefficients involved in the above equations were estimated for the first time. Predictions on the survival time of SARS coronavirus in different temperature scale were then performed. It was found theoretically that, such survival time falls in an extremely wide range, say from several seconds in high temperature to an almost infinitely long time in a low temperature environment, which has already or is being supported by the currently available tests data. Applications of the present theory to interpret several existing phenomena were presented and their implementations in developing new technical ways for SARS prevention and clinical therapy were discussed. Uncertainties involved in the theoretical models were also analyzed and predicted. Parametric studies were performed to test the effects of the rate coefficients to the survival time of SARS coronavirus. Some important factors, which can significantly vary the denaturation or replication process of SARS coronavirus were pointed out. Through regulating the parameters involved in the equation, certain potential therapies either through drug delivery or engineering approach to treat the SARS disease can possibly be established. Extension of the present model for further studies was also suggested. This study opens a new theoretical way for probing into the complex behaviors of SARS coronavirus. Modellierung der Denaturierung oder Repliziryng von SARS-Korona-Viren Zusammenfassung Der Kenntnisstand über die Eigenschaften des in 2003 neu aufgetretenen SARS Korona Virus, der einige Hundert Menschenleben gekostet hat, ist relativ gering. Die Ermittlung des Denaturierungs- und Replizierungsmechanismuses des SARS Virus ist für seine Bekämpfung von hoher Bedeutung. Experimentelle Untersuchungen an diesem extrem gefährlichen Virus dürfen nur durch Laboratorien mit einem hohen Sicherheitsstandard erfolgen. Die Vorhersage des Verhaltens des SARS Virus in unterschiedlichen Umgebungsbedingungen ist dabei erforderlich. In der vorliegenden Studie wird die überlebensdauer des Virus unter Labor- und realen Bedingungen durch Anwendung der bekannten Arrhenius-Beziehung für temperaturabhängige Vorgänge ermittelt. Das physikalische und chemische Verhalten des SARS Virus wird anhand der zugrundeliegenden Modell- Parameter beschrieben. Basierend auf den ersten Messungen von Mitgliedern des WHO-laboratory-network über die Stabilität und Widerstandsfähigkeit des Virus wurden erstmalig die Geschwindigkeitskoeffizienten des Berechnungsmodells bestimmt. Vorhersagen der Überlebensdauer des SARS-Virus unter unterschiedlichen Temperaturbedingungen wurden ausgeführt. Das sich hieraus ergebende, sehr unterschiedliche Ausmaß der Überlebensfähigkeit in Abhängigkeit der Umgebungstemperatur ist durch den Vergleich mit verfügbaren experimentellen Ergebnissen bestätigt worden. Die Anwendung der vorgestellten Modellierung zur Interpretation realer Phänomene und zur Entwicklung technischer Maßnahmen zur Vorbeugung und klinischen Therapierung von SARS wird diskutiert. Der Einfluß von Unsicherheiten des Modells wird analysiert und abgeschätzt. Parametrische Studien sind durchgeführt worden, um den Einfluß der Geschwindigkeitskoeffizienten auf die Überlebensdauer des SARS Virus darzustellen. Einige wichtige Einflußgrößen auf die Denaturierung und Replikationsfähigkeit des SARS Virus werden aufgezeigt. Durch eine Variation der Modellparameter kann die potentielle Wirksamkeit medikamentöser oder physikalischer Therapien abgeschätzt werden. Erweiterungsmöglichkeiten des vorgestellten Modells werden vorgeschlagen. Die vorliegende Studie ermöglicht neue, theoretische Vorgehensweisen zur Untersuchung des komplexen Verhaltensmusters des SARS Virus.

negative: MMDB: annotating protein sequences with Entrez's 3D-structure database Three-dimensional (3D) structure is now known for a large fraction of all protein families. Thus, it has become rather likely that one will find a homolog with known 3D structure when searching a sequence database with an arbitrary query sequence. Depending on the extent of similarity, such neighbor relationships may allow one to infer biological function and to identify functional sites such as binding motifs or catalytic centers. Entrez's 3D-structure database, the Molecular Modeling Database (MMDB), provides easy access to the richness of 3D structure data and its large potential for functional annotation. Entrez's search engine offers several tools to assist biologist users: (i) links between databases, such as between protein sequences and structures, (ii) pre-computed sequence and structure neighbors, (iii) visualization of structure and sequence/structure alignment. Here, we describe an annotation service that combines some of these tools automatically, Entrez's ‘Related Structure’ links. For all proteins in Entrez, similar sequences with known 3D structure are detected by BLAST and alignments are recorded. The ‘Related Structure’ service summarizes this information and presents 3D views mapping sequence residues onto all 3D structures available in MMDB ().

negative: Geographic Distribution and Risk Factors of the Initial Adult Hospitalized Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in Mainland China BACKGROUND: As of 31(st) March 2010, more than 127,000 confirmed cases of 2009 pandemic influenza A (H1N1), including 800 deaths, were reported in mainland China. The distribution and characteristics of the confirmed cases in the initial phase of this pandemic in this country are largely unknown. The present study aimed to characterize the geographic distribution and patient characteristics of H1N1 infection in the 2009 pandemic as well as to identify potential risk factors associated with adverse patient outcome in China, through retrospective analyses of 885 hospitalized cases with confirmed H1N1 infection. METHODOLOGY/PRINCIPAL FINDINGS: The proportional hazards model was employed to detect risk factors for adverse outcome; the geo-statistical maps were used to characterize the distribution of all 2668 confirmed H1N1 patients throughout mainland China. The number of new cases increased slowly in May, 2009, but rapidly between June and August of the year. Confirmed cases were reported in 26 provinces; Beijing, Guangdong, Shanghai, Zhejiang and Fujian were the top five regions of the incidence of the virus infection. After being adjusted for gender, age, chronic pulmonary disease and other general symptoms, delay for more than two days before hospital admission (HR: 0.6; 95%CI: 0.5–0.7) and delayed onset of the H1N1-specific respiratory symptoms (HR: 0.3; 95%CI: 0.2–0.4) were associated with adverse patient outcome. CONCLUSIONS/SIGNIFICANCE: The 2009 pandemic influenza A affected east and southeast coastal provinces and most populous cities more severely than other regions in mainland China due to higher risk of high level traffic-, high population density-, and high population mobility-associated H1N1 transmission.The clinical symptoms were mild in the initial phase of infection. Delayed hospital admission and delayed appearance of respiratory symptoms were among the major risk factors for poor patient outcome. These findings may have significant implications in the future pandemic preparedness and response.

negative: Dose‐dependent Inhibition of Gynecophoral Canal Protein Gene Expression in Vitro in the Schistosome (Schistosoma japonicum) by RNA Interference Abstract The gynecophoral canal protein gene SjGCP of Schistosoma japonicum that is necessary for the pairing between the male and female worms is specifically expressed in the adult male worm. This protein is widely distributed in the adult female worm after pairing. Reverse transcription‐polymerase chain reaction (RT‐PCR) and immunofluorescence were employed to analyze the relationship between the RNAi effect and dsRNA dosage in the parasites. The results revealed that the inhibition of SjGCP expression by siRNA is dose‐dependent. RT‐PCR analysis showed that the SjGCP transcript level was reduced by 75% when 100 nM dsRNA was applied. Edited by: Wang‐Yi LIU

negative: Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients Background: As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males. Methods: From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen. Findings: The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another died patient was 67 years old, who died in March 10, 2020 and tissue sample via testicular biopsy was tested negative for viral RNA. Conclusion: No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.

negative: Impact of non-pharmaceutical interventions on documented cases of COVID-19 Background: The novel coronavirus (SARS-CoV-2) has rapidly evolved into a global epidemic. To control its spread, countries have implemented non pharmaceutical interventions (NPIs), such as school or border closures, while others have even enforced complete lockdowns. Here we study the impact of NPIs in reducing documented cases of COVID-19. Documented case numbers are selected because they are essential for decision-makers in the area of health-policy when monitoring and evaluating current control mechanisms. Methods: We empirically estimate the relative reduction in the number of new cases attributed to each NPI. A cross-country analysis is performed using documented cases through April 15, 2020 from n=20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland). Results: As of April 15, venue closures were associated with a reduction in the number of new cases by 36 % (95% credible interval [CrI] 20-48 %), closely followed by gathering bans (34 %; 95% CrI 21-45 %), border closures (31 %; 95% CrI 19-42 %), and work bans on non-essential business activities (31 %; 95% CrI 16-44 %). Event bans lead to a slightly less pronounced reduction (23 %; 95% CrI 8-35 %). School closures (8 %; 95% CrI 0-23 %) and lockdowns (5 %; 95% CrI 0-14 %) appeared to be the least effective among the NPIs considered in this analysis. Conclusions: With this cross-country analysis, we provide early estimates regarding the impact of different NPIs for controlling the COVID-19 epidemic. These findings are relevant for evaluating current health-policies. Keywords: COVID-19, coronavirus, non-pharmaceutical interventions, policy measures, health-policy, public health, health services research

negative: COVID-19 in patients with lung cancer BACKGROUND: Patients with lung cancers may have disproportionately severe COVID-19 outcomes. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n=102) at a single center from March 12-May 6, 2020. Thresholds of severity were defined a priori as hospitalization, ICU/intubation/DNI (a composite metric of severe disease including ICU stay, intubation and invasive mechanical ventilation, and/or transition to do not intubate [DNI]), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. HLA alleles were inferred from MSK-IMPACT (n=46) and compared to controls with lung cancer and no known non-COVID-19 (n=5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer-deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease (Odds ratios for severe COVID-19 2.9, 95% CI 1.07-9.44 comparing the median [23.5 pack-years] to never and 3.87, 95% CI 1.35-9.68, respectively). Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. HLA supertypes were generally similar in mild or severe cases of COVID-19 compared to non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

negative: BIP4COVID19: Releasing impact measures for articles relevant to COVID-19 Since the beginning of the 2019-20 coronavirus pandemic, a large number of relevant articles has been published or become available in preprint servers. These articles, along with earlier related literature, compose a valuable knowledge base affecting contemporary research studies, or even government actions to limit the spread of the disease and treatment decisions taken by physicians. However, the number of such articles is increasing at an intense rate making the exploration of the relevant literature and the identification of useful knowledge in it challenging. In this work, we describe BIP4COVID19, an open dataset compiled to facilitate the coronavirus-related literature exploration, by providing various indicators of scientific impact for the relevant articles. Finally, we provide a publicly accessible Web interface on top of our data, allowing the exploration of the publications based on the computed indicators.

negative: Radiotherapy imaging: an unexpected ally in fighting COVID 19 pandemic

negative: Automatic Detection of Coronavirus Disease (COVID-19) in X-ray and CT Images: A Machine Learning-Based Approach The newly identified Coronavirus pneumonia, subsequently termed COVID-19, is highly transmittable and pathogenic with no clinically approved antiviral drug or vaccine available for treatment. The most common symptoms of COVID-19 are dry cough, sore throat, and fever. Symptoms can progress to a severe form of pneumonia with critical complications, including septic shock, pulmonary edema, acute respiratory distress syndrome and multi-organ failure. While medical imaging is not currently recommended in Canada for primary diagnosis of COVID-19, computer-aided diagnosis systems could assist in the early detection of COVID-19 abnormalities and help to monitor the progression of the disease, potentially reduce mortality rates. In this study, we compare popular deep learning-based feature extraction frameworks for automatic COVID-19 classification. To obtain the most accurate feature, which is an essential component of learning, MobileNet, DenseNet, Xception, ResNet, InceptionV3, InceptionResNetV2, VGGNet, NASNet were chosen amongst a pool of deep convolutional neural networks. The extracted features were then fed into several machine learning classifiers to classify subjects as either a case of COVID-19 or a control. This approach avoided task-specific data pre-processing methods to support a better generalization ability for unseen data. The performance of the proposed method was validated on a publicly available COVID-19 dataset of chest X-ray and CT images. The DenseNet121 feature extractor with Bagging tree classifier achieved the best performance with 99% classification accuracy. The second-best learner was a hybrid of the a ResNet50 feature extractor trained by LightGBM with an accuracy of 98%.

negative: Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19) To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.

negative: Clinical Distancing and Mitigation of Coronavirus Disease 2019 Social distancing as a technique to limit transmission of infectious disease has come into common parlance following the arrival and rapid spread of a novel coronavirus disease around the world in 2019 and 2020. But in the face of an emerging pandemic threat, it is crucial that we start to apply these principles to the clinic, the emergency department, and the hospital ward. We propose that this dynamic situation calls for a parallel “Clinical Distancing” in which we as a medical culture go against many of our fundamental instincts and, at least in the short term, begin to reduce unnecessary patient-care contacts for the benefit of our patients and our ability to continue to provide care to those who need it most. In this commentary, we provide specific recommendations for the rapid implementation of clinical distancing techniques.

negative: Chapter 9 Recovery from Infection This chapter addresses the factors involved in recovery from infection. Antibody and cellular responses (CMI) are considered. The mechanisms by which antibodies neutralise viruses/prevent infection are described, as is the involvement of antibody in bacterial and protozoal diseases. The role of CMI in recovery from specific bacterial, protozoal and viral infections is considered. The mechanisms of cell killing by cytotoxic T-cells is described and the role of NK cells and macrophages in pathogen clearance is discussed, as is the role of inflammation. Mechanisms by which the complement system acts and its role in vivo is discussed, as is the interferon response. Recovery from S. typhimurium is used to illustrate the multimechanistic nature of recovery. The role of temperature in recovery and pathogen factors that induce fever are considered. Tissue repair mechanisms are discussed, as is finally resistance to infection.

negative: Computational analysis of SARS-CoV-2/COVID-19 surveillance by wastewater-based epidemiology locally and globally: Feasibility, economy, opportunities and challenges Abstract With the economic and practical limits of medical screening for SARS-CoV-2/COVID-19 coming sharply into focus worldwide, scientists are turning now to wastewater-based epidemiology (WBE) as a potential tool for assessing and managing the pandemic. We employed computational analysis and modeling to examine the feasibility, economy, opportunities and challenges of enumerating active coronavirus infections locally and globally using WBE. Depending on local conditions, detection in community wastewater of one symptomatic/asymptomatic infected case per 100 to 2,000,000 non-infected people is theoretically feasible, with some practical successes now being reported from around the world. Computer simulations for past, present and emerging epidemic hotspots (e.g., Wuhan, Milan, Madrid, New York City, Teheran, Seattle, Detroit and New Orleans) identified temperature, average in-sewer travel time and per-capita water use as key variables. WBE surveillance of populations is shown to be orders of magnitude cheaper and faster than clinical screening, yet cannot fully replace it. Cost savings worldwide for one-time national surveillance campaigns are estimated to be in the million to billion US dollar range (US$), depending on a nation's population size and number of testing rounds conducted. For resource poor regions and nations, WBE may represent the only viable means of effective surveillance. Important limitations of WBE rest with its inability to identify individuals and to pinpoint their specific locations. Not compensating for temperature effects renders WBE data vulnerable to severe under-/over-estimation of infected cases. Effective surveillance may be envisioned as a two-step process in which WBE serves to identify and enumerate infected cases, where after clinical testing then serves to identify infected individuals in WBE-revealed hotspots. Data provided here demonstrate this approach to save money, be broadly applicable worldwide, and potentially aid in precision management of the pandemic, thereby helping to accelerate the global economic recovery that billions of people rely upon for their livelihoods.

negative: Estimation of the Probability of Reinfection With COVID-19 by the Susceptible-Exposed-Infectious-Removed-Undetectable-Susceptible Model BACKGROUND: With the sensitivity of the polymerase chain reaction test used to detect the presence of the virus in the human host, the worldwide health community has been able to record a large number of the recovered population. OBJECTIVE: The aim of this study was to evaluate the probability of reinfection in the recovered class and the model equations, which exhibits the disease-free equilibrium state for the coronavirus disease. METHODS: The model differential equation was evaluated for the disease-free equilibrium for the case of reinfection as well as the existence and stability criteria for the disease, using the model proportions. This evaluation shows that the criteria for a local or worldwide asymptotic stability with a basic reproductive number (R0=0) were satisfied. Hence, there is a chance of no secondary reinfections from the recovered population, as the rate of incidence of the recovered population vanishes (ie, B=0). RESULTS: With a total of about 900,000 infected cases worldwide, numerical simulations for this study were carried out to complement the analytical results and investigate the effect that the implementation of quarantine and observation procedures has on the projection of further virus spread. CONCLUSIONS: As shown by the results, the proportion of the infected population, in the absence of a curative vaccination, will continue to grow worldwide; meanwhile, the recovery rate will continue slowly, which means that the ratio of infection rate to recovery rate will determine the death rate that is recorded. Most significant for this study is the rate of reinfection by the recovered population, which will decline to zero over time as the virus is cleared clinically from the system of the recovered class.

negative: SARS‐associated viral hepatitis caused by a novel coronavirus: Report of three cases Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (Hepatology 2004;39:302–310.)

negative: COVID-19 Pandemic in the Italian Population: Validation of a Post-Traumatic Stress Disorder Questionnaire and Prevalence of PTSD Symptomatology Since December 2019, the COVID-19 pandemic has attracted worldwide attention for its rapid and exponential diffusion. The long-term psychological impact, of both the spread of the virus and the restrictive policies adopted to counteract it, remains uncertain. However, recent studies reported a high level of psychological distress and Post-Traumatic Stress Disorder (PTSD) symptoms. The purpose of this study is to assess the psychometric properties of a new questionnaire, to evaluate PTSD risk related to the COVID-19 emergency. A total of Italian people completed a web-based cross-sectional survey broadcasted through different social-media. Demographic data and some psychological dimensions, such as general distress and sleep disturbance, were collected. A new self-report questionnaire (COVID-19-PTSD), consisting of 19 items, was developed starting from the PTSD Check List for DSM-5 (PCL-5) questionnaire, and it was administered in order to analyze its psychometric properties. The results highlighted the adequate psychometric properties of the COVID-19-PTSD questionnaire. The confirmatory factor analysis indicated that a seven-factor model (Intrusion, Avoidance, Negative Affect, Anhedonia, Dysphoric arousal, Anxious arousal and Externalizing behavior) best fits the data. Significant correlations were found among COVID-19-PTSD scores, general distress and sleep disturbance. A high percentage of PTSD symptomatology (29.5%) was found in the Italian population. COVID-19-PTSD appears to be effective in evaluating the specific stress symptoms related to the COVID-19 pandemic in the Italian population. These results are relevant from a clinical point of view because they suggest that the COVID-19 pandemic could be considered as a traumatic event. Psychological interventions to counteract short- and long-term psychopathological effects, consequent to the COVID-19 pandemic, appear to be necessary.

negative: No evidence of SARS-CoV-2 in semen of males recovering from COVID-19 Abstract Objective To describe detection of SARS-CoV-2 in seminal fluid of patients recovering from COVID-19 and describe the expression profile of ACE2 and TMPRSS2 within the testicle. Design observational, cross-sectional study Setting Tertiary referral center Patients Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples Intervention None Main Outcome Measures Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. Results Six patients (19%) demonstrated scrotal discomfort concerning for viral orchitis around the time of COVID-19 confirmation. SARS-CoV-2 was not detected in semen after a median of 31 days (IQR: 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. Conclusions SARS-CoV-2 was not detected in the semen of patients recovering from COVID-19 one month after COVID-19 diagnosis. ACE2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

negative: Association of Personal Protective Equipment Use with Successful Protection Against COVID-19 Infection Among Health Care Workers The coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. In order to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs, we conducted a molecular epidemiological study among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. Nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) detection were performed to confirm SARS-CoV-2 infection among those HCWs. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 15, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. These HCWs were provided with adequate supply of PPE as committed by their original institutions or provinces. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. In conclusion, our findings indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection.

negative: How did the U.S. stock market recover from the Covid-19 contagion?

negative: Remdesivir data offer hope, with caveats Gilead Sciences’ experimental antiviral remdesivir helped people with COVID-19 recover faster, according to limited data released on April 29 from a trial led by the US National Institute of Allergy and Infectious Diseases The Food and Drug Administration is expected in the coming days to take the unprecedented step of issuing an emergency use authorization, which will make the drug more readily available for stockpiling The study by NIAID, which is part of the National Institutes of Health, is considered to be the highest quality among the myriad Phase III trials testing remdesivir’s effectiveness against COVID-19, the disease caused by the novel coronavirus Unlike most other trials, it includes a placebo arm, a part of a trial’s design that scientists rely on for a clear signal of a treatment’s worth The trial enrolled 1,063 people, 20% of whom received the standard of care rather than remdesivir The primary end point View: PDF ;Full Text HTML

negative: Clinical Validation of a SARS-CoV-2 Real-Time Reverse Transcription PCR Assay Targeting the Nucleocapsid Gene BACKGROUND: Detection of SARS-CoV-2 viral RNA is important for the diagnosis and management of COVID-19. METHODS: We present a clinical validation of a RT-PCR assay for the SARS-CoV-2 nucleocapsid (N1) gene. Offboard lysis on an automated nucleic acid extraction system (EMAG®) was optimized with endemic Coronaviruses (OC43 and NL63). Genomic RNA and SARS-CoV-2 RNA in a recombinant viral protein coat (Accuplex) were used as control materials and compared for recovery from nucleic acid extraction. RESULTS: Nucleic acid extraction showed decreased recovery of endemic Coronavirus in vitro transcribed RNA (NL63) compared to attenuated virus (OC43). SARS-CoV-2 RNA (Accuplex) had more reliable recovery from extraction through amplification compared to genomic RNA. Recovery of genomic RNA was improved by combining lysis buffer with clinical matrix prior to adding RNA. The RT-PCR assay demonstrated 100% in silico sensitivity and specificity. The accuracy across samples was 100% (75 of 75). Precision studies showed 100% intra-run, inter-run, and inter-technologist concordance. The limit of detection was 264 copies per ml (estimated 5 copies per reaction; 35.56 mean Ct value). CONCLUSIONS: This SARS-CoV-2 assay demonstrates appropriate characteristics for use under an emergency use authorization. Endemic Coronavirus controls were useful in optimizing the extraction procedure. In the absence of live or attenuated virus, recombinant virus in a protein coat is an appropriate control specimen type for assay validation during a pandemic.

negative: Survival of Respiratory Viruses on Fresh Produce In addition to enteric viruses of fecal origin, emerging zoonotic viruses such as respiratory coronaviruses and influenza viruses may potentially be transmitted via contaminated foods. The goal of this study was to determine the recovery efficiencies and the survival of two respiratory viruses, namely, adenovirus 2 (Ad2) and coronavirus 229E (CoV229E), on fresh produce in comparison to the enteric poliovirus 1 (PV1). Adenovirus was recovered with efficiencies of 56.5, 31.8, and 34.8 % from lettuce, strawberries, and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6 % yet could not be recovered from strawberries. Poliovirus was recovered with efficiencies of 76.7 % from lettuce, but only 0.06 % from strawberries. For comparison purposes, the survival of Ad2, CoV229E, and PV1 was determined for periods up to 10 days on produce. The enteric PV1 survived better than both respiratory viruses on lettuce and strawberries, with only ≤1.03 log(10) reductions after 10 days of storage at 4 °C compared to CoV229E not being recovered after 4 days on lettuce and reductions of 1.97 log(10) and 2.38 log(10) of Ad2 on lettuce and strawberries, respectively, after 10 days. Nevertheless, these respiratory viruses were able to survive for at least several days on produce. There is therefore the potential for transfer to the hands and subsequently to the mucosa via rubbing the eyes or nose. In addition, some respiratory coronaviruses (e.g., severe acute respiratory syndrome coronavirus) and adenoviruses are also capable of replication in the gut and there is thus some potential for acquisition through the consumption of contaminated produce.

negative: An Update on Current Therapeutic Drugs Treating COVID-19 The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2.

negative: Visible Insights of the Invisible Pandemic: A Scientometric, Altmetric and Topic Trend Analysis The recent SARS-COV-2 virus outbreak has created an unprecedented global health crisis! The disease is showing alarming trends with the number of people getting infected with this disease, new cases and death rate are all highlighting the need to control this disease at the earliest. The strategy now for the governments around the globe is how to limit the spread of the virus until the research community develops treatment/drug or vaccination against the virus. The outbreak of this disease has unsurprisingly led to huge volume of research within a short period of time surrounding this disease. It has also led to aggressive social media activity on twitter, Facebook, dedicated blogs, news reports and other online sites actively involved in discussing about the various aspects of and related to this disease. It becomes a useful and challenging exercise to draw from this huge volume of research, the key papers that form the research front, its influence in the research community, and other important research insights. Similarly, it becomes important to discern the key issues that influence the society concerning this disease. The paper is motivated by this. It attempts to distinguish which are the most influential papers, the key knowledge base and major topics surrounding the research covered by COVID-19. Further it attempts to capture the society's perception by discerning key topics that are trending online. The study concludes by highlighting the implications of this study.

negative: A predictive model for Covid-19 spread applied to eight US states A compartmental epidemic model is proposed to predict the Covid-19 virus spread. It considers: both detected and undetected infected populations, medical quarantine and social sequestration, release from sequestration, plus possible reinfection. The coefficients in the model are evaluated by fitting to empirical data for eight US states: Arizona, California, Florida, Illinois, Louisiana, New Jersey, New York State, and Texas. Together these states make up 43% of the US population; some of these states appear to have handled their initial outbreaks well, while others appear to be emerging hotspots. The evolution of Covid-19 is fairly similar among the states: variations in contact and recovery rates remain below 5%; however, not surprisingly, variations are larger in death rate, reinfection rate, stay-at-home effect, and release rate from sequestration. The results reveal that outbreaks may have been well underway in several states before first detected and that California might have seen more than one influx of the pandemic. Our projections based on the current situation indicate that Covid-19 will become endemic, spreading for more than two years. Should states fully relax stay-at-home orders, most states may experience a secondary peak in 2021. If lockdowns had been kept in place, the number of Covid-19 deaths so far could have been significantly lower in most states that opened up. Additionally, our model predicts that decreasing contact rate by 10%, or increasing testing by approximately 15%, or doubling lockdown compliance (from the current $\sim$ 15% to $\sim$ 30%) will eradicate infections in the state of Texas within a year. Extending our fits for all of the US states, we predict about 11 million total infections (including undetected), 8 million cumulative confirmed cases, and 630,000 cumulative deaths by November 1, 2020.

negative: A preliminary study on the reproductive toxicity of GS-5734 on male mice The authors have withdrawn their manuscript given that some conclusions need more research and data support. In addition, they intend to improve the experimental design to make the research more rigorous. If you have any questions, please contact the corresponding author.

negative: Modeling COVID-19 Epidemic in Heilongjiang Province, China The Coronavirus Disease 2019 (COVID-19) surges worldwide. However, massive imported patients especially into Heilongjiang Province in China recently have been an alert for local COVID-19 outbreak. We collected data from January 23 to March 25 from Heilongjiang province and trained an ordinary differential equation model to fit the epidemic data. We extended the simulation using this trained model to characterize the effect of an imported ‘escaper’. We showed that an imported ‘escaper’ was responsible for the newly confirmed COVID-19 infections from Apr 9 to Apr 19 in Heilongjiang province. Stochastic simulations further showed that significantly increased local contacts among imported ‘escaper’, its epidemiologically associated cases and susceptible populations greatly contributed to the local outbreak of COVID-19. Meanwhile, we further found that the reported number of asymptomatic patients was markedly lower than model predictions implying a large asymptomatic pool which was not identified. We further forecasted the effect of implementing strong interventions immediately to impede COVID-19 outbreak for Heilongjiang province. Implementation of stronger interventions to lower mutual contacts could accelerate the complete recovery from coronavirus infections in Heilongjiang province. Collectively, our model has characterized the epidemic of COVID-19 in Heilongjiang province and implied that strongly controlled measured should be taken for infected and asymptomatic patients to minimize total infections.

negative: COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs In the Wuhan Province of China, in December 2019, the novel coronavirus 2019 (COVID-19) has caused a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. Subsequently, coronavirus 2 (SARS-CoV-2) provoked a pandemic which is considered a life-threatening disease. The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

negative: Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China BACKGROUND: A novel coronavirus was identified in December, 2019 in Wuhan, China, and traditional Chinese medicine (TCM) played an active role in combating the novel coronavirus pneumonia (NCP) caused by this fast-spreading virus COVID-19. Thus, we aimed to explore TCM characteristics of clinical efficacy to NCP, as well as to optimize Qingfei Paidu decoction (QFPDD) and the recommended formulas to NCP by National Health Commission (NHC). METHODS: Chinese medical sciences theory and clinical application of TCM were analyzed. A total of 54 NCP patients were observed in a hospital from Wuhan, whose clinical characteristics and utilization of Chinese Medicines (CMs) were described. Paired t test was used to measure the change of patients’ hemogram during hospitalization period, indicating the effect of CMs. Multiple linear regression analysis was applied to explore the factors affecting the length of hospital stay. Network pharmacology analysis was applied to figure out the performance of NHC-recommended formulas of five disease stages at levels of compounds, targets and pathways. RESULT: The average length of hospital stay was 8.96 days. Patients over 45 stayed 9.79 days in hospital in average, longer than 7.64 days of patients under 45. Comparing the hemograms between admission and discharge of hospital, the number of leukocytes, neutrophil, lymphocyte and platelet increased, while the numbers of erythrocytes, hemoglobin concentration and hematocrit decreased. According to the standard coefficients of regression, the factor affecting the length of stay for the most was CMs in category of invigorating spleen and removing dampness (ISRD), followed by administrating CMs, male, and cough. Thirty-two CMs were screened after deleting duplication from QFPDD and NHC-recommended formulas. Compound quercetin, luteolin, kaempferol, acacetin etc., were all involved in the treatment of various disease stages on the compound level both in generality and individuality. CONCLUSION: TCM has a systemic theoretical understanding on the pathological evolution and a positive clinical efficacy on NCP. The CMs of ISRD improved patients’ recovery, suggesting the importance of regulating intestinal function and keeping microenvironmental balance in TCM treatment of NCP. The active compounds from QFPDD and NHC-recommended formulas contribute to recovery of varied disease progresses during TCM treating NCP.

negative: Mitigating the wider health effects of covid-19 pandemic response

negative: Drugs supply and pharmaceutical care management practices at a designated hospital during the COVID-19 epidemic Abstract The coronavirus disease-19 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus that was first detected at the end of December 2019. The epidemic has affected various regions of China in different degrees. As the situations evolve, the COVID-19 had been confirmed in many countries, and made a assessment that it can be characterized as a pandemic by the World Health Organization on March 11, 2020. Drugs are the main treatment of COVID-19 patients. Pharmaceutical service offers drug safety ensurance for COVID-19 patients. According to COVID-19 prevention and control policy and requirements, combined with series of diagnosis and treatment plans, pharmacists in the first provincial-level COVID-19 diagnosis and treatment unit in Jilin Province in Northeast China have established the management practices of drug supply and pharmaceutical care from four aspects: personnel, drugs supply management, off-label drug use management and pharmaceutical care. During the outbreak, the pharmaceutical department of THJU completed its assigned workload to ensure drug supply. So far, no nosocomial infections and medication errors have occurred, which has stabilized the mood of the staff and boosted the pharmacists' confidence in fighting the epidemic. For the treatment of COVID-19, pharmacists conducted adverse reaction monitoring and participated in the multidisciplinary consultation of COVID-19. Up to now, the COVID-19 patients admitted to THJU have not shown any new serious adverse reactions and been cured finally. The hospital pharmacy department timely adjusted the work mode, and the formed management practices is a powerful guarantee for the prevention and control of the COVID-19 epidemic. This paper summarized the details and practices of drug supply and pharmaceutical services management to provide experience for the people who involving in COVID-19 prevention and contain in other abroad epidemic areas.

negative: Novel coronavirus disease (COVID-19) in children Coronavirus disease (COVID-19) was firstly reported at the end of 2019. The disease rapidly spread all around the world in a few months and was declared a worldwide pandemic by WHO in March 2020. By April 9, there were 1,436,198 confirmed COVID-19 cases in the world, nearly with 6% mortality rate. This novel infectious disease causes respiratory tract illness that may generally occur as mild upper respiratory tract disease or pneumonia. In older patients and/or patients with underlying conditions, it may result in acute respiratory distress syndrome, multi organ failure and even death. According to the current literature, children account approximately for 1%–5% of diagnosed COVID-19 cases. Generally, COVID-19 seems to be a less severe disease for children than adults. Approximately 90% of pediatric patients are diagnosed as asymptomatic, mild, or moderate disease. However, up to 6.7% of cases may be severe. Severe illness is generally seen in patients smaller than 1 year of age and patients who have underlying disesases. The epidemiological and clinical patterns of COVID-19 and treatment approaches in pediatric patients still remain unclear although many pediatric reports are published. This review aims to summarize the current epidemics, clinical presentations, diagnosis, and treatment of COVID-19 in pediatric patients.

negative: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.

negative: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question "What rehabilitation services do survivors of COVID-19 require?" The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.

negative: Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection Abstract Background The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. Methods We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. Findings Of the 34 operative patients, the median age was 55 years (IQR, 43–63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. Interpretation In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%. Funding National Natural Science Foundation of China.

negative: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020 A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1] On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2] Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID-19) As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3-5] Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020 The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission %R doi:https://doi org/10 2807/1560-7917 ES 2020 25 9 2000178

negative: The six-minute walk test as a measure of postoperative recovery after colorectal resection: further examination of its measurement properties. INTRODUCTION Patients, clinicians and researchers seek an easy, reproducible and valid measure of postoperative recovery. The six-minute walk test (6MWT) is a low-cost measure of physical function, which is a relevant dimension of recovery. The aim of the present study was to contribute further evidence for the validity of the 6MWT as a measure of postoperative recovery after colorectal surgery. METHODS This study involved a sample of 174 patients enrolled in three previous randomized controlled trials. Construct validity was assessed by testing the hypotheses that the distance walked in 6 min (6MWD) at 4 weeks after surgery is greater (1) in younger versus older patients, (2) in patients with higher preoperative physical status versus lower, (3) after laparoscopic versus open surgery, (4) in patients without postoperative complications versus with postoperative complications; and that 6MWD (5) correlates cross-sectionally with self-reported physical activity as measured with a questionnaire (CHAMPS). Statistical analysis was performed using linear regression and Spearman's correlation. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to guide the formulation of hypotheses and reporting of results. RESULTS One hundred and fifty-one patients who completed the 6MWT at 4 weeks after surgery were included in the analysis. All hypotheses tested for construct validity were supported by the data. Older age, poorer physical status, open surgery and occurrence of postoperative complications were associated with clinically relevant reduction in 6MWD (>19 m). There was a moderate positive correlation between 6MWD and patient-reported physical activity (r = 0.46). CONCLUSIONS This study contributes further evidence for the construct validity of the 6MWT as a measure of postoperative recovery after colorectal surgery. Results from this study support the use of the 6MWT as an outcome measure in studies evaluating interventions aimed to improve postoperative recovery.

negative: Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.

negative: Espen expert statements and practical guidance on clinical nutrition in COVID-19 patients

negative: Long term complications and rehabilitation of COVID-19 patients. With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.

negative: Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis Objective: To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). Design: Retrospective case studies Setting: 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants: 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measures: Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results: Of the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P<0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. Conclusion: Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes.

negative: Long-Term Persistence of IgG Antibodies in SARS-CoV Infected Healthcare Workers BACKGROUND: The ongoing worldwide outbreak of the 2019-nCoV is markedly similar to the severe acute respiratory syndrome (SARS) outbreak 17 years ago. During the 2002-2003 SARS outbreak, healthcare workers formed a special population of patients. Although virus-specific IgG play important roles in virus neutralization and prevention against future infection, limited information is available regarding the long term persistence of IgG after infection with SARS-like coronavirus. METHODS: A long-term prospective cohort study followed 34 SARS-CoV-infected healthcare workers from a hospital with clustered infected cases during the 2002-2003 SARS outbreak in Guangzhou, China, with a 13-year follow-up. Serum samples were collected annually from 2003-2015. Twenty SARS-CoV-infected and 40 non-infected healthcare workers were enrolled in 2015, and their serum samples were collected. All sera were tested for IgG antibodies with ELISA using whole virus and a recombinant nucleocapsid protein of SARS-CoV, as a diagnostic antigen. RESULTS: Anti SARS-CoV IgG was found to persist for up to 12 years. IgG titers typically peaked in 2004, declining rapidly from 2004-2006, and then continued to decline at a slower rate. IgG titers in SARS-CoV-infected healthcare workers remained at a significantly high level until 2015. Patients treated with corticosteroids at the time of infection were found to have lower IgG titers than those without. CONCLUSIONS: IgG antibodies against SARS-CoV can persist for at least 12 years. The presence of SARS-CoV IgG might provide protection against SARS-CoV and other betacoronavirus. This study provides valuable information regarding humoral immune responses against SARS-CoV and the 2019-nCoV.

negative: Practice considerations on the use of investigational anti-COVID-19 medications: Dosage, administration and monitoring WHAT IS KNOWN AND OBJECTIVE: Understanding investigational medications is important. Many older drugs are being investigated for repurposing against COVID-19. We comment on various drugs currently undergoing such trials to optimize their safe use. COMMENT: We describe medications used during early COVID-19 outbreaks in South Korea, focusing on practice aspects including the method of drug administration, drug formulation, patient-monitoring for adverse reactions and drug interactions informed by our experience during the 2015 outbreak of Middle East respiratory syndrome (MERS). We comment on hydroxychloroquine, chloroquine, lopinavir/ritonavir with zinc supplement, remdesivir, tocilizumab, ciclesonide, niclosamide and high-dose intravenous immunoglobulin (IVIG). WHAT IS NEW AND CONCLUSION: Effective therapies are urgently needed to manage COVID-19, and existing drugs such as antivirals and antimalarials are under investigation for repurposing to meet this need. This process requires up-to-date drug information to ensure optimum use, particularly safety and efficacy profiles of the medications, until convincing evidence is reported.

negative: The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19 Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.

negative: Modelling the downhill of the Sars-Cov-2 in Italy and a universal forecast of the epidemic in the world In a previous article [1] we have described the temporal evolution of the Sars- Cov-2 in Italy in the time window February 24-April 1. As we can see in [1] a generalized logistic equation captures both the peaks of the total infected and the deaths. In this article our goal is to study the missing peak, i.e. the currently infected one (or total currently positive). After the April 7 the large increase in the number of swabs meant that the logistical behavior of the infected curve no longer worked. So we decided to generalize the model, introducing new parameters. Moreover, we adopt a similar approach used in [1] (for the estimation of deaths) in order to evaluate the recoveries. In this way, introducing a simple conservation law, we define a model with 4 populations: total infected, currently positives, recoveries and deaths. Therefore, we propose an alternative method to a classical SIRD model for the evaluation of the Sars-Cov-2 epidemic. However, the method is general and thus applicable to other diseases. Finally we study the behavior of the ratio infected over swabs for Italy, Germany and USA, and we show as studying this parameter we recover the generalized Logistic model used in [1] for these three countries. We think that this trend could be useful for a future epidemic of this coronavirus.

negative: Battle Buddies: Rapid Deployment of a Psychological Resilience Intervention for Health Care Workers During the Coronavirus Disease 2019 Pandemic The outbreak of the coronavirus disease 2019 (COVID-19) and its rapid global spread have created unprecedented challenges to health care systems. Significant and sustained efforts have focused on mobilization of personal protective equipment, intensive care beds, and medical equipment, while substantially less attention has focused on preserving the psychological health of the medical workforce tasked with addressing the challenges of the pandemic. And yet, similar to battlefield conditions, health care workers are being confronted with ongoing uncertainty about resources, capacities, and risks; as well as exposure to suffering, death, and threats to their own safety. These conditions are engendering high levels of fear and anxiety in the shortterm, and place individuals at risk for persistent stressexposure syndromes, subclinical mental health symptoms, and professional burnout in the longterm. Given the potentially wide-ranging mental health impact of COVID-19, protecting health care workers from adverse psychological effects of the pandemic is critical. Therefore, we present an overview of the potential psychological stress responses to the COVID-19 crisis in medical providers and describe preemptive resilience-promoting strategies at the organizational and personal level. We then describe a rapidly deployable Psychological Resilience Intervention founded on a peersupport model (Battle Buddies) developed by the United States Army. This intervention—the product of a multidisciplinary collaboration between the Departments of Anesthesiology and Psychiatry & Behavioral Sciences at the University of Minnesota Medical Center—also incorporates evidence-informed “stress inoculation” methods developed for managing psychological stress exposure in providers deployed to disasters. Our multilevel, resource-efficient, and scalable approach places 2 key tools directly in the hands of providers: (1) apeersupport Battle Buddy; and (2) adesignated mental health consultant who can facilitate training in stress inoculation methods, provide additional support, or coordinate referral for external professional consultation. In parallel, we have instituted a voluntary research data-collection component that will enable us to evaluate the intervention’s effectiveness while also identifying the most salient resilience factors for future iterations. It is our hope that these elements will provide guidance to other organizations seeking to protect the well-being of their medical workforce during the pandemic. Given the remarkable adaptability of human beings, we believe that, by promoting resilience, our diverse health care workforce can emerge from this monumental challenge with new skills, closer relationships, and greater confidence in the power of community.

negative: No Clear Benefit to the Use of Corticosteroid as Treatment in Adult Patients with Coronavirus Disease 2019 : A Retrospective Cohort Study Background Coronavirus disease 2019 (COVID-19) is becoming an increasing global health issue which has spread across the globe. We aimed to study the effect of corticosteroids in the treatment of adult inpatients with COVID-19. Methods A retrospective cohort of 115 consecutive adult COVID-19 patients admitted to The Third Peoples Hospital of Hubei Province between Jan 18, 2020, and Feb 28, 2020 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, clinical features, laboratory indicators and clinical outcomes. The primary endpoint was defined as either mortality or intensive care unit (ICU) admission. Known adverse prognostic factors were used as covariates in multiple logistic regressions to adjust for their confounding effects on outcomes. Results Among 115 patients, 73 patients (63.5%) received corticosteroid. The levels of age, C-reactive protein, D-dimer and albumin were similar in both groups. The corticosteroid group had more adverse outcomes (32.9% vs. 11.9%) and statistically significant differences were observed (p=0.013). In multivariate analysis, corticosteroid treatment was associated with a 2.155-fold increase in risk of either mortality or ICU admission, although not statistically significant. Conclusion No evidence suggests that adult patients with COVID-19 will benefit from corticosteroids, and they might be more likely to be harmed with such treatment.

negative: Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study BACKGROUND: The ongoing epidemics of coronavirus disease 2019 (COVID-19) have caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. METHODS: We conducted a case-control study to compare clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. RESULTS: During January 24 to February 29, 2020, there were sixteen pregnant women with confirmed COVID-19 pneumonia and eighteen suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest took cesarean section. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest CT images of COVID-19 pneumonia. Compared to the controls, COVID-19 pneumonia patients had lower counts of white blood cells (WBC), neutrophils, C-reactive protein (CRP), and alanine aminotransferase (ALT) on admission. Increased levels of WBC, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. There were three (18.8%) and three (16.7%) of the mothers with confirmed or suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than the control group. None experienced respiratory failure during hospital stay. COVID-19 infection was not found in the newborns and none developed severe neonatal complications. CONCLUSION: Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal delivery or caesarean section. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

negative: SARS-CoV-2 can induce brain and spine demyelinating lesions SARS-CoV-2 can attack the central nervous system in the early stages of infection. Headache, anosmia, and dysgeusia are common symptoms. Disturbance of consciousness and seizures can occur as complications in case of severe COVID-19. We described the case of a COVID-19 patient admitted for interstitial pneumonia and seizures. MRI showed newly diagnosed demyelinating lesions. High-dose steroid treatment allowed neurological and respiratory recovery. We speculated a delayed immune response induced by SARS-CoV-2. The virus may lead to a SIRS-like immune disorder or play a role of infective trigger. Prompt invasive treatment should be adopted to avoid hypoxic neurotoxicity and prevent CNS injuries.

negative: Population anxiety and positive behaviour change during the COVID-19 epidemic: Cross-sectional surveys in Singapore, China and Italy Background On 31 December 2019, an epidemic of pneumonia of unknown aetiology was first reported in the city of Wuhan, Hubei Province, People's Republic of China. A rapidly progressing epidemic of COVID-19 ensued within China, with multiple exportations to other countries. We aimed to measure perceptions and responses towards COVID-19 in three countries to understand how population-level anxiety can be mitigated in the early phases of a pandemic. Methods Between February and March 2020, we conducted online surveys in Singapore, China and Italy with a total of 4,505 respondents to measure knowledge, perceptions, anxiety and behaviours towards the COVID-19 epidemic, and identified factors associated with lower anxiety and more positive behavioural responses. Findings Respondents reported high awareness of COVID-19 and its accompanying symptoms, comparable information seeking habits and similarly high levels of information sufficiency, adherence to and acceptance of public health control measures. Higher self-efficacy was associated with lower anxiety levels in all three countries, while willingness to comply with restrictive measures and greater information sufficiency were associated with more positive behavioural changes to reduce spread of infection. Interpretation Population-level anxiety and behavioural responses to an outbreak can be influenced by information provided. This should be used to inform future outbreak preparedness plans, taking into account the importance of increasing population-level self-efficacy and information sufficiency to reduce anxiety and promote positive behavioural changes. Funding This was supported by the Saw Swee Hock School of Public Health, the Department of Communications and New Media, National University of Singapore, and the National Medical Research Council, Singapore

negative: Feasibility Study of Mitigation and Suppression Intervention Strategies for Controlling COVID-19 Outbreaks in London and Wuhan Recent outbreaks of coronavirus disease 2019 (COVID-19) has led a global pandemic cross the world. Most countries took two main interventions: suppression like immediate lockdown cities at epicentre or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both strategies have their apparent merits and limitations; it becomes extremely hard to conduct one intervention as the most feasible way to all countries. Targeting at this problem, this paper conducted a feasibility study by defining a mathematical model named SEMCR that can access effectiveness of mitigation, suppression and hybrid interventions for controlling COVID-19 outbreaks in London and Wuhan. It extended traditional SEIR (Susceptible-Exposed Infectious-Recovered) model by adding two key features: a direct connection between Exposed and Recovered populations, and separating infections into mild and critical cases. It defined parameters to classify two stages of COVID-19 control: active contain by isolation of cases and contacts, passive contain by suppression or mitigation. The model was fitted and evaluated with public dataset containing daily number of confirmed active cases including Wuhan and London during January, 2020 and March 2020. The simulated results showed that 1) Immediate suppression taken in Wuhan significantly reduced the total exposed and infectious populations to 119610, but it has to be consistently maintained at least 90 days (by the middle of April 2020). Its success heavily relied on sufficiently external support from other places of China. This mode were not suitable to other countries that have no sufficient health resources. 2) In London, it is possible to take a hybrid intervention of suppression and mitigation for every 2 or 3 weeks over a longer period to balance the total infections and economic loss. While the total infectious populations in this scenario would be possibly 2 times than the one taking suppression, economic loss and recovery of London would be less affected. 3) Both in Wuhan and London cases, one important issue of fitting practical data was that there were a large portion (probably 62.9% in Wuhan) of self-recovered populations that were asymptomatic or mild symptomatic. These people might think they have been healthy at home and did not go to hospital for COVID-19 tests. Early release of intervention intensity potentially increased a risk of the second outbreak. One limitation of our model was that our prediction of infections and deaths depended on a parameter estimation of intervention intensity that presented by average number contacts with susceptible individuals as infectious individuals in a certain region. It assumed that each intervention had equivalent effects on the reproduction number R in different regions over time. Practical effectiveness of implementing intervention intensity might be varied with respect to cultures or other issues of certain county.

negative: Long-term sequelae of SARS in children Summary Severe acute respiratory syndrome (SARS) runs a more benign course in children during the acute phase. Unlike adult patients, no fatalities were reported among the paediatric SARS patients. Published data on long-term sequelae of SARS are very limited. In our follow-up study, although patients have clinically recovered from their initial illness, exercise impairment and residual radiological abnormalities were demonstrated at 6 months after diagnosis. It is important to assess these patients on a regular basis to detect and provide appropriate management for persistent or emerging long-term sequelae in the physical, psychological and social domains.

negative: Political Intrusions into the International Health Regulations Treaty and Its Impact on Management of Rapidly Emerging Zoonotic Pandemics: What History Tells Us For a large number of health care providers world-wide, the coronavirus disease 2019 (COVID-19) pandemic is their first experience in population-based care. In past decades, lower population densities, infectious disease outbreaks, epidemics, and pandemics were rare and driven almost exclusively by natural disasters, predatory animals, and war. In the early 1900s, Sir William Osler first advanced the knowledge of zoonotic diseases that are spread from reservoir animals to human animals. Once rare, they now make up 71% or more of new diseases. Globally, zoonotic spread occurs for many reasons. Because the human population has grown in numbers and density, the spread of these diseases accelerated though rapid unsustainable urbanization, biodiversity loss, and climate change. Furthermore, they are exacerbated by an increasing number of vulnerable populations suffering from chronic deficiencies in food, water, and energy. The World Health Organization (WHO) and its International Health Regulation (IHR) Treaty, organized to manage population-based diseases such as Influenza, severe acute respiratory syndrome (SARS), H1N1, Middle East respiratory syndrome (MERS), HIV, and Ebola, have failed to meet population-based expectations. In part, this is due to influence from powerful political donors, which has become most evident in the current COVID-19 pandemic. The global community can no longer tolerate an ineffectual and passive international response system, nor tolerate the self-serving political interference that authoritarian regimes and others have exercised over the WHO. In a highly integrated globalized world, both the WHO with its IHR Treaty have the potential to become one of the most effective mechanisms for crisis response and risk reduction world-wide. Practitioners and health decision-makers must break their silence and advocate for a stronger treaty, a return of the WHO’s singular global authority, and support highly coordinated population-based management. As Osler recognized, his concept of “one medicine, one health” defines what global public health is today.

negative: Clinical Features of COVID-19-Related Liver Damage Abstract Background & Aims Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Methods We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. Results Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P=.027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09±4.79 days) than patients with normal liver function (12.76±4.14 days) (P=.021). Conclusions More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

negative: Less Wrong COVID-19 Projections With Interactive Assumptions COVID-19 pandemic is an enigma with uncertainty caused by biological and health systems factors. Although many models have been developed all around the world, transparent models that allow interacting with the assumptions will become more important as we test various strategies for lockdown, testing and social interventions and enable effective policy decisions. In this paper we developed a suite of models to guide development of policies under different scenarios when the lockdown opens. These had been deployed to create an interactive dashboard called COVision which includes the Agent based Models (ABM) and classical compartmental models i.e Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) approaches. Our tool allows simulation of scenarios by changing strength of lockdown, basic reproduction number(R0), asymptomatic spread, testing rate, contact rate (Beta), recovery rate (Gamma), incubation period and starting number of cases. We optimized ABMs and classical compartmental models to fit the actual data, both of which performed well in terms of R-squared, root mean squared error (RMSE) and mean absolute percentage error (MAPE). Out of the three models in our suite, ABM was able to capture the data better than SIR and SEIR and achieved an RSQ of 92.3% for India and 89% for Maharashtra for the next 30 days. We also computed R0 using SIR and SEIR models which were found to be decreasing over the different periods of lockdown indicating the effectiveness of policies and interventions. Finally, we formulated ICU bed requirements using our best models. Our evaluation suggests that ABM models were able to capture the dynamic nature of the epidemic for a longer duration of time while classical SIR and SEIR models performed inefficiently for longer terms. The visual interactivity and ability to simulate outcomes under different parameters will allow the policymakers to make informed decisions for estimating the strength of lockdown to be implemented and testing rates. Further, our models were able to highlight the differences at state level for the parameters such as R0 and contact rates and hence can be applied for state specific decision making. An interactive dashboard http://covision.tavlab.iiitd.edu.in have been hosted as a web-server for the war level monitoring of the covid19 pandemic in India in public domain

negative: Covering coronavirus—emerging tools for the fight against the common enemy

negative: RNA Virus Reverse Genetics and Vaccine Design RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.

negative: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic BACKGROUND: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. FINDINGS: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. INTERPRETATION: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

negative: Greening the Post-pandemic Recovery in the G20 Rebuilding G20 economies after the COVID-19 pandemic requires rethinking what type of economy we need and want in the future. Simply reviving the existing ‘brown’ economy will exacerbate irreversible climate change and other environmental risks. For G20 economies, investing in a workable and affordable green transition is essential. A good place to start is learning what worked and what did not from previous efforts to green the economic recovery during the 2008–2009 Great Recession, examining the cases of the United States and South Korea. Policies for a sustained economic recovery amount to much more than just short-term fiscal stimulus. Transitioning from fossil fuels to a sustainable low-carbon economy will require long-term commitments (5–10 years) of public spending and pricing reforms. The priorities for public spending include support for private sector green innovation and infrastructure, development of smart grids, transport systems, charging station networks, and sustainable cities. Pricing carbon and pollution, and removing fossil-fuel subsidies, can accelerate the transition, raise revenues for the necessary public investments, and lower the overall cost of the green transition.

negative: Overview of Covid-19; its prevention and management in the light of Unani medicine Abstract Since December 2019, a respiratory pandemic, named as coronavirus disease 2019 (Covid-19) caused by a new coronavirus named as SARS-CoV-2, has taken the world by storm. The symptoms are fever, malaise, and cough which resolve in a few days in most cases; but may progress to respiratory distress and organ failure. Transmission is through droplet infection or fomites, but other modes such as airborne transmission and oro-fecal transmission is also speculated. Research is underway to develop effective vaccines and medicines for the disease. In such a scenario, we present the measures described in Unani system of medicine for health protection during epidemics. Unani is a traditional system of medicine developed during the middle ages, which employs natural drugs of herbal, animal and mineral origin for treatment. In Unani medicine, during an epidemic, apart from isolation and quarantine, three measures are of utmost importance, (i) purification of surroundings using certain herbal drugs as fumigants or sprays, (ii) health promotion and immune-modulation, and (iii) use of health-protecting drugs and symptom-specific drugs. Drugs such as loban (Styrax benzoides W. G. Craib), sandroos (Hymenaea verrucosa Gaertn.) za'fran (Crocus sativus L.), vinegar etc. are prescribed in various forms. Scientific researches on these drugs reveal the presence of a number of pharmacologically active substances, which may provide a new insight into the management of infections and epidemics.

negative: COVID-19 and pets: When pandemic meets panic Abstract As the novel coronavirus outbreak spreads globally with devastating effects on human health, pets are also becoming unnecessary victims amidst the pandemic panic. Many have been reluctantly left home alone by owners who have been forced to temporarily evacuate their homes. And, although no evidence exists to indicate that they can either transmit the virus or develop its associated coronavirus disease 2019 (COVID-19), fear among the public that pets might play a role in spreading COVID-19 has resulted in pets being abandoned or even killed. This article outlines some of the ways in which the current pandemic has negatively impacted the welfare of pets. It also highlights the relationships between animal, human, and environmental health, as well as the importance of taking a collaborative transdisciplinary One Health approach to help prevent future COVID-19 outbreaks.

negative: Validation of a Self-administrable, Saliva-based RT-qPCR Test Detecting SARS-CoV-2 Background: Rapid and easy COVID-19 diagnostic testing is essential to controlling the pandemic and facilitating safe resumption of clinical care, employment and other social activities. Methods: This study was conducted to validate an self-administrable saliva-based RT-qPCR test for the SARS-CoV2 virus under controlled laboratory conditions (analytical validation) according to federal guidance. An additional clinical study assessed positive (n=34) and negative (n=57) nasopharyngeal swab samples collected contemporaneously with saliva samples. Assessments for analytical specificity, sensitivity, cross reactivity and sample stability to simulate shipping conditions were conducted. Results: Positive and negative agreement with third-party laboratory results were reported as 97.1% and 96.5-98.2%, respectively. Limit of detection was established at 5 copies/L. Stability through simulated shipping conditions found 100% concordance up to 56 hours after collection. Discussion: These data validate a self-collected saliva-based COVID-19 RT-qPCR assay that performs comparably well to an assay of health care-provider administered nasopharyngeal swab samples. Accordingly, the United States Food and Drug Administration granted emergency use authorization in June 2020. Use of the saliva-based assay overcomes barriers to the necessary widespread testing, including strained health care resources, supply chain disruptions of laboratory materials, testing and protective equipment and exposure risks due to close interpersonal contact.

negative: Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing COVID-19 caused by SARS-CoV-2 has recently affected over 200,000 people and killed more than 8000. Immune system dysregulation such as lymphopenia and inflammatory cytokine storm has been observed in COVID-19 patients, but it remains unclear for the change of key immune cell subsets and their states during COVID-19. Here, we applied single-cell technology to comprehensively characterize transcriptional changes of peripheral blood mononuclear cells in ten patients recovered from COVID-19. Compared with healthy control, COVID-19 induced a unique signature of immune cells in humans, especially in the early recovery stage (ERS). In ERS patients, T cells were decreased remarkably, while monocytes were increased. A detailed analysis of monocytes showed that there was an increased ratio of classical CD14++ monocytes with highly inflammatory genes expression, as well as a greater abundance of CD14++IL1B+ monocytes. For nature killer (NK) cells and T cells, CD4+ T cells were significantly decreased and expressed high level of inflammatory markers, while NK cells were increased. In addition, T cells were highly expanded clone, especially in CD4+ T memory cells and CD8+ T cells. Among B cells, plasma cells were increased remarkably, and naïve B cells were reduced. Our study also identified several novel B cell receptor (BCR) changes (such as IGHV1-8 and IGHV3-7), and confirmed isotypes (IGKV3-11 and IGHV3-21) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23+IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicated that IL-1B and M-CSF may be novel candidate target gene for inflammatory storm, and TNFSF13, IL-18 and IL-4 may be benefit for the recovery of COVID-19 patients. Our study provides the first evidence of inflammatory immune signature in early recovery stage, suggesting that the COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccine and antibodies for the treatment of COVID-19.

negative: Detecting fake news for the new coronavirus by reasoning on the Covid-19 ontology In the context of the Covid-19 pandemic, many were quick to spread deceptive information. I investigate here how reasoning in Description Logics (DLs) can detect inconsistencies between trusted medical sources and not trusted ones. The not-trusted information comes in natural language (e.g."Covid-19 affects only the elderly"). To automatically convert into DLs, I used the FRED converter. Reasoning in Description Logics is then performed with the Racer tool.

negative: Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review At the end of 2019 a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing severe acute respiratory syndrome expanded globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus a global pandemic. We performed a narrative review to describe existing literature with regard to Corona Virus Disease 2019 (COVID-19) epidemiology, pathophysiology, diagnosis, management and future perspective. MEDLINE, EMBASE and Scopus databases were searched for relevant articles. Although only when the pandemic ends it will be possible to assess the full health, social and economic impact of this global disaster, this review represents a picture of the current state of the art. In particular, we focus on public health impact, pathophysiology and clinical manifestations, diagnosis, case management, emergency response and preparedness.

negative: Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine OBJECTIVES: Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine. METHODS: A swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed. RESULTS: Throughout 4 days of normothermic support, extracorporeal lung function was maintained (arterial oxygen tension/inspired oxygen fraction >400 mm Hg; compliance >20 mL/cm H(2)O), and recipient swine were hemodynamically stable (lactate <3 mmol/L; pH, 7.42 ± 0.05). Radiography revealed well-aerated lower lobes and consolidation in upper lobes of extracorporeal lungs, and bronchoscopy showed healthy airways without edema or secretions. In bronchoalveolar lavage fluid, granulocyte-macrophage colony-stimulating factor, interleukin (IL) 4, IL-6, and IL-10 levels increased less than 6-fold, whereas interferon gamma, IL-1α, IL-1β, IL-1ra, IL-2, IL-8, IL-12, IL-18, and tumor necrosis factor alpha levels decreased from baseline to day 4. Histologic evaluations confirmed an intact blood–gas barrier and outstanding preservation of airway and alveolar architecture. Cellular viability and metabolism in extracorporeal lungs were confirmed after 4 days. CONCLUSIONS: We demonstrate feasibility of normothermic maintenance of extracorporeal lungs for 4 days by cross-circulation with conscious swine. Cross-circulation approaches could support the recovery of damaged lungs and enable organ bioengineering to improve transplant outcomes.

negative: Predicting the impacts of epidemic outbreaks on global supply chains: A simulation-based analysis on the coronavirus outbreak (COVID-19/SARS-CoV-2) case Abstract Epidemic outbreaks are a special case of supply chain (SC) risks which is distinctively characterized by a long-term disruption existence, disruption propagations (i.e., the ripple effect), and high uncertainty. We present the results of a simulation study that opens some new research tensions on the impact of COVID-19 (SARS-CoV-2) on the global SCs. First, we articulate the specific features that frame epidemic outbreaks as a unique type of SC disruption risks. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of epidemic outbreaks on the SC performance using the example of coronavirus COVID-19 and anyLogistix simulation and optimization software. We offer an analysis for observing and predicting both short-term and long-term impacts of epidemic outbreaks on the SCs along with managerial insights. A set of sensitivity experiments for different scenarios allows illustrating the model’s behavior and its value for decision-makers. The major observation from the simulation experiments is that the timing of the closing and opening of the facilities at different echelons might become a major factor that determines the epidemic outbreak impact on the SC performance rather than an upstream disruption duration or the speed of epidemic propagation. Other important factors are lead-time, speed of epidemic propagation, and the upstream and downstream disruption durations in the SC. The outcomes of this research can be used by decision-makers to predict the operative and long-term impacts of epidemic outbreaks on the SCs and develop pandemic SC plans. Our approach can also help to identify the successful and wrong elements of risk mitigation/preparedness and recovery policies in case of epidemic outbreaks. The paper is concluded by summarizing the most important insights and outlining future research agenda.

negative: Severe Thrombocytopenia in a Patient with COVID-19. Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm³ and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.

negative: COVID-19 and smoking: A systematic review of the evidence COVID-19 is a coronavirus outbreak that initially appeared in Wuhan, Hubei Province, China, in December 2019, but it has already evolved into a pandemic spreading rapidly worldwide(1,2). As of 18 March 2020, a total number of 194909 cases of COVID-19 have been reported, including 7876 deaths, the majority of which have been reported in China (3242) and Italy (2505)(3). However, as the pandemic is still unfortunately under progression, there are limited data with regard to the clinical characteristics of the patients as well as to their prognostic factors(4). Smoking, to date, has been assumed to be possibly associated with adverse disease prognosis, as extensive evidence has highlighted the negative impact of tobacco use on lung health and its causal association with a plethora of respiratory diseases(5). Smoking is also detrimental to the immune system and its responsiveness to infections, making smokers more vulnerable to infectious diseases(6). Previous studies have shown that smokers are twice more likely than non-smokers to contract influenza and have more severe symptoms, while smokers were also noted to have higher mortality in the previous MERS-CoV outbreak(7,8). Given the gap in the evidence, we conducted a systematic review of studies on COVID-19 that included information on patients’ smoking status to evaluate the association between smoking and COVID-19 outcomes including the severity of the disease, the need for mechanical ventilation, the need for intensive care unit (ICU) hospitalization and death. The literature search was conducted on 17 March 2020, using two databases (PubMed, ScienceDirect), with the search terms: [‘smoking’ OR ‘tobacco’ OR ‘risk factors’ OR ‘smoker*’] AND [‘COVID-19’ OR ‘COVID 19’ OR ‘novel coronavirus’ OR ‘sars cov-2’ OR ‘sars cov 2’] and included studies published in 2019 and 2020. Further inclusion criteria were that the studies were in English and referred to humans. We also searched the reference lists of the studies included. A total of 71 studies were retrieved through the search, of which 66 were excluded after full-text screening, leaving five studies that were included. All of the studies were conducted in China, four in Wuhan and one across provinces in mainland China. The populations in all studies were patients with COVID-19, and the sample size ranged from 41 to 1099 patients. With regard to the study design, retrospective and prospective methods were used, and the timeframe of all five studies covered the first two months of the COVID-19 pandemic (December 2019, January 2020). Specifically, Zhou et al.(9) studied the epidemiological characteristics of 191 individuals infected with COVID-19, without, however, reporting in more detail the mortality risk factors and the clinical outcomes of the disease. Among the 191 patients, there were 54 deaths, while 137 survived. Among those that died, 9% were current smokers compared to 4% among those that survived, with no statistically significant difference between the smoking rates of survivors and non-survivors (p=0.21) with regard to mortality from COVID-19. Similarly, Zhang et al.(10) presented clinical characteristics of 140 patients with COVID-19. The results showed that among severe patients (n=58), 3.4% were current smokers and 6.9% were former smokers, in contrast to non-severe patients (n=82) among which 0% were current smokers and 3.7% were former smokers , leading to an OR of 2.23; (95% CI: 0.65–7.63; p=0.2). Huang et al.(11) studied the epidemiological characteristics of COVID-19 among 41 patients. In this study, none of those who needed to be admitted to an ICU (n=13) was a current smoker. In contrast, three patients from the non-ICU group were current smokers, with no statistically significant difference between the two groups of patients (p=0.31), albeit the small sample size of the study. The largest study population of 1099 patients with COVID-19 was provided by Guan et al.(12) from multiple regions of mainland China. Descriptive results on the smoking status of patients were provided for the 1099 patients, of which 173 had severe symptoms, and 926 had non-severe symptoms. Among the patients with severe symptoms, 16.9% were current smokers and 5.2% were former smokers, in contrast to patients with non-severe symptoms where 11.8% were current smokers and 1.3% were former smokers. Additionally, in the group of patients that either needed mechanical ventilation, admission to an ICU or died, 25.5% were current smokers and 7.6% were former smokers. In contrast, in the group of patients that did not have these adverse outcomes, only 11.8% were current smokers and 1.6% were former smokers. No statistical analysis for evaluating the association between the severity of the disease outcome and smoking status was conducted in that study. Finally, Liu et al.(13) found among their population of 78 patients with COVID-19 that the adverse outcome group had a significantly higher proportion of patients with a history of smoking (27.3%) than the group that showed improvement or stabilization (3.0%), with this difference statistically significant at the p=0.018 level. In their multivariate logistic regression analysis, the history of smoking was a risk factor of disease progression (OR=14.28; 95% CI: 1.58–25.00; p= 0.018). We identified five studies that reported data on the smoking status of patients infected with COVID-19. Notably, in the largest study that assessed severity, there were higher percentages of current and former smokers among patients that needed ICU support, mechanical ventilation or who had died, and a higher percentage of smokers among the severe cases(12). However, from their published data we can calculate that the smokers were 1.4 times more likely (RR=1.4, 95% CI: 0.98–2.00) to have severe symptoms of COVID-19 and approximately 2.4 times more likely to be admitted to an ICU, need mechanical ventilation or die compared to non-smokers (RR=2.4, 95% CI: 1.43–4.04). In conclusion, although further research is warranted as the weight of the evidence increases, with the limited available data, and although the above results are unadjusted for other factors that may impact disease progression, smoking is most likely associated with the negative progression and adverse outcomes of COVID-19.

negative: Mathematical Modeling of the Spread of COVID-19 in Moscow and Russian Regions To model the spread of COVID-19 coronavirus in Russian regions and in Moscow, a discrete logistic equation describing the increase in the number of cases is used. To check the adequacy of the mathematical model, the simulation results were compared with the spread of coronavirus in China, in a number of European and Asian countries, and the United States. The parameters of the logistics equation for Russia, Moscow and other large regions were determined in the interval (01.03 - 08.04). A comparative analysis of growth rates of COVID-19 infected population for different countries and regions is presented. Various scenarios of the spread of COVID-19 coronavirus in Moscow and in the regions of Russia are considered. For each scenario, curves for the daily new cases and graphs for the increase in the total number of cases were obtained, and the dynamics of infection spread by day was studied. Peak times, epidemic periods, the number of infected people at the peak and their growth were determined.

negative: Abstracts from the International Symposium on Frontiers in Life Sciences: Molecular Basis of Disease, Prevention and Treatment

negative: Posttraumatic Stress after SARS Posttraumatic stress disorder (PTSD) can arise in patients with medical illness. We used 2 Chinese self-report measures to examine features of PTSD, anxiety, and depression in 131 survivors of severe acute respiratory syndrome at 1 month and 3 months after discharge from the hospital. Risk factors associated with psychological distress were identified.

negative: Aspects cliniques, physiopathologiques, et thérapeutiques de la sclérose en plaques Multiple sclerosis (MS) is characterized by multiple demyelinating lesions disseminated in the central nervous system. The clinical course of MS involves acute attacks leading to permanent disability and a chronic progressive stage occurring at the beginning of the disease or after a relapsing-remitting phase. Investigations that provide supportive evidence for the diagnosis of MS are magnetic resonance imaging and cerebrospinal fluid examination. Recent pathological studies showed evidence of early axonal pathology, remyelination in some cases, and diffuse pathology. Genetic and immunological studies suggest that MS is an auto-immune disease, partially genetically determined but the role of an environmental factor, possibly infectious is possible. Cumulative evidence of the efficacy of interferon beta and other disease-modifying drug therapy has completely modified the therapeutic approach of MS.

negative: COVID-19: Updated Data and its Relation to the Cardiovascular System. In December 2019, a new human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) by the World Health Organization, emerged in the city of Wuhan, China. Spreading globally, it is now considered pandemic, with approximately 3 million cases worldwide at the end of April. Its symptoms include fever, cough, and headache, but the main one is shortness of breath. In turn, it is believed that there is a relationship between COVID-19 and damage to the heart muscle, and hypertensive and diabetic patients, for example, seem to have worse prognosis. Therefore, COVID-19 may worsen in individuals with underlying adverse conditions, and a not negligible number of patients hospitalized with this virus had cardiovascular or cerebrovascular diseases. Systemic inflammatory response and immune system disorders during disease progression may be behind this association. In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell. There is, however, no scientific evidence to support the interruption of these drugs. Since they are fundamental for certain chronic diseases, the risk and benefit of their withdrawal in this scenario should be carefully weighed. Finally, cardiologists and health professionals should be aware of the risks of infection and protect themselves as much as possible, sleeping properly and avoiding long working hours.

negative: Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis Abstract Objective To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19. Methods We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2 . Publication bias was assessed using Egger's test. Results 43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4–87.7]), cough (60.3% [54.2–66.3]), and fatigue (38.0% [29.8–46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2–78.2]), decreased lymphocyte count (57.4% [44.8–69.5]) and increased lactate dehydrogenase (51.6% [31.4–71.6]). Ground-glass opacities (80.0% [67.3–90.4]) and bilateral pneumonia (73.2% [63.4–82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender. Conclusions The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.

negative: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.

negative: 2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution.

negative: Low-density lipoprotein is a potential predictor of poor prognosis in patients with coronavirus disease 2019 Abstract Background The pandemic of coronavirus disease 2019 (COVID-19) has become a global threat to public health. The lipid pathophysiology in COVID-19 is unknown. Methods In this retrospective longitudinal study, we monitored the serum lipids in 17 surviving and 4 non-surviving COVID-19 cases prior to their viral infections and duration the entire disease courses. Results In surviving cases, the low-density lipoprotein (LDL) levels decreased significantly on admission as compared with the levels before infection; the LDL levels remained constantly low during the disease progression and resumed to the original levels when patients recovered (pre-infection: 3.5 (3.0–4.4); on admission: 2.8 (2.3–3.1), p < .01; progression: 2.5 (2.3–3.0); discharge: 3.6 (2.7–4.1); median (IQR), in mmol/L). In non-surviving patients, LDL levels showed an irreversible and continuous decrease until death (1.1 (0.9–1.2), p = .02 versus the levels on admission). The ratio changes of LDL levels inversely correlated with ratio changes of high-sensitivity C-reactive protein levels. Logistic regression analysis showed increasing odds of lowered LDL levels associated with disease progression (odds ratio: 4.48, 95% IC: 1.55–12.92, p = .006) and in-hospital death (odds ratio: 21.72, 95% IC: 1.40–337.54, p = .028). Conclusions LDL levels inversely correlated to disease severities, which could be a predictor for disease progress and poor prognosis.

negative: Follow-up studies in COVID-19 recovered patients - is it mandatory? Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.

negative: Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City Background: Little is known about factors associated with hospitalization and critical illness in Covid-19 positive patients. Methods: We conducted a cross-sectional analysis of all patients with laboratory-confirmed Covid-19 treated at a single academic health system in New York City between March 1, 2020 and April 2, 2020, with follow up through April 7, 2020. Primary outcomes were hospitalization and critical illness (intensive care, mechanical ventilation, hospice and/or death). We conducted multivariable logistic regression to identify risk factors for adverse outcomes, and maximum information gain decision tree classifications to identify key splitters. Results: Among 4,103 Covid-19 patients, 1,999 (48.7%) were hospitalized, of whom 981/1,999 (49.1%) have been discharged home, and 292/1,999 (14.6%) have died or were discharged to hospice. Of 445 patients requiring mechanical ventilation, 162/445 (36.4%) have died. Strongest hospitalization risks were age [≥]75 years (OR 66.8, 95% CI, 44.7-102.6), age 65-74 (OR 10.9, 95% CI, 8.35-14.34), BMI>40 (OR 6.2, 95% CI, 4.2-9.3), and heart failure (OR 4.3 95% CI, 1.9-11.2). Strongest critical illness risks were admission oxygen saturation <88% (OR 6.99, 95% CI 4.5-11.0), d-dimer>2500 (OR 6.9, 95% CI, 3.2-15.2), ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2), and C-reactive protein (CRP) >200 (OR 5.78, 95% CI, 2.6-13.8). In the decision tree for admission, the most important features were age >65 and obesity; for critical illness, the most important was SpO2<88, followed by procalcitonin >0.5, troponin <0.1 (protective), age >64 and CRP>200. Conclusions: Age and comorbidities are powerful predictors of hospitalization; however, admission oxygen impairment and markers of inflammation are most strongly associated with critical illness.

negative: Successful treatment of plasma exchange followed by intravenous immunogloblin in a critically ill patient with 2019 novel coronavirus infection Abstract We report a case of a laboratory-confirmed 2019 novel coronavirus infected (known as COVID-19) patient who developed respiratory failure and shock accompanied by persistent diarrhoea despite conventional therapeutic interventions. The patient avoided mechanical ventilation and acquired an immediate clinical and radiological improvement, after treatment of intensive plasma exchange (PE) followed by intravenous immunogloblin (IVIG). Successful therapeutic strategies in our case suggest timely initiating PE treatment followed by IVIG in critically ill patients with COVID-19 may prevent the disease from worsening and help to reduce the requirements for mechanical ventilation and intensive supportive care. What's more, it may improve poor clinical outcomes of these patients.

negative: Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1–12·3) days. The shedding durations were longer than previous estimates (3·9–7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes.

negative: Understanding the COVID19 Outbreak: A Comparative Data Analytics and Study The Coronavirus, also known as the COVID-19 virus, has emerged in Wuhan China since late November 2019. Since that time, it has been spreading at large-scale until today all around the world. It is currently recognized as the world's most viral and severe epidemic spread in the last twenty years, as compared to Ebola 2014, MERS 2012, and SARS 2003. Despite being still in the middle of the outbreak, there is an urgent need to understand the impact of COVID-19. The objective is to clarify how it was spread so fast in a short time worldwide in unprecedented fashion. This paper represents a first initiative to achieve this goal, and it provides a comprehensive analytical study about the Coronavirus. The contribution of this paper consists in providing descriptive and predictive models that give insights into COVID-19 impact through the analysis of extensive data updated daily for the outbreak in all countries. We aim at answering several open questions: How does COVID-19 spread around the world? What is its impact in terms of confirmed and death cases at the continent, region, and country levels? How does its severity compare with other epidemic outbreaks, including Ebola 2014, MERS 2012, and SARS 2003? Is there a correlation between the number of confirmed cases and death cases? We present a comprehensive analytics visualization to address the questions mentioned above. To the best of our knowledge, this is the first systematic analytical papers that pave the way towards a better understanding of COVID-19. The analytical dashboards and collected data of this study are available online [1].

negative: Considerations for interactions of drugs used for the treatment of COVID-19 with anti-Cancer treatments SARS-CoV2 infection is an emerging issue worldwide. Cancer patient are at increased risk of infection compared to general population. On the other hand, these patients are at major risk of drug interactions caused by renal and hepatic impairment background. Because of the long-term use of chemotherapy drugs, drug interactions are important in these patients especially with SARS-CoV2 treatments now. This paper is review of reported drug interactions of current treatments for COVID-19 and anticancer agents.

negative: Modeling the Effective Control Strategy for Transmission Dynamics of Global Pandemic COVID-19 The novel coronavirus disease (namely COVID-19) has taken attention because of its deadliness across the globe, causing a massive death as well as critical situation around the world. It is an infectious disease which is caused by newly discovered coronavirus. Our study demonstrates with a nonlinear model of this devastating COVID-19 which narrates transmission from human-to-human in the society. Pontryagin Maximum principle has also been applied in order to obtain optimal control strategies where the maintenance of social distancing is the major control. The target of this study is to find out the most fruitful control measures of averting coronavirus infection and eventually, curtailed of the COVID-19 transmission among people. The model is investigated analytically by using most familiar necessary conditions of Pontryagin maximum principle. Furthermore, numerical simulations have been performed to illustrate the analytical results. The analysis reveals that implementation of educational campaign, social distancing and developing human immune system are the major factors which can be able to plunge the scenario of becoming infected.

negative: Influence of airborne transmission of SARS-CoV-2 on COVID-19 pandemic. A review In recent years, a number of epidemiological studies have demonstrated that exposure to air pollution is associated with several adverse outcomes, such as acute lower respiratory infections, chronic obstructive pulmonary disease, asthma, cardiovascular diseases, and lung cancer among other serious diseases. Air pollutants such as sulfur oxides, nitrogen oxides, carbon monoxide and dioxide, particulate matter (PM), ozone and volatile organic compounds (VOCs) are commonly found at high levels in big cities and/or in the vicinity of different chemical industries. An association between air concentrations of these pollutants and human respiratory viruses interacting to adversely affect the respiratory system has been also reported. The present review was aimed at assessing the potential relationship between the concentrations of air pollutants on the airborne transmission of SARS-CoV-2 and the severity of COVID-19 in patients infected by this coronavirus. The results of most studies here reviewed suggest that chronic exposure to certain air pollutants leads to more severe and lethal forms of COVID-19 and delays/complicates the recovery of patients of this disease.

negative: Visual Data Analysis and Simulation Prediction for COVID-19 The COVID-19 (formerly, 2019-nCoV) epidemic has become a global health emergency, as such, WHO declared PHEIC. China has taken the most hit since the outbreak of the virus, which could be dated as far back as late November by some experts. It was not until January 23rd that the Wuhan government finally recognized the severity of the epidemic and took a drastic measure to curtain the virus spread by closing down all transportation connecting the outside world. In this study, we seek to answer a few questions: How did the virus get spread from the epicenter Wuhan city to the rest of the country? To what extent did the measures, such as, city closure and community quarantine, help controlling the situation? More importantly, can we forecast any significant future development of the event had some of the conditions changed? By collecting and visualizing publicly available data, we first show patterns and characteristics of the epidemic development; we then employ a mathematical model of disease transmission dynamics to evaluate the effectiveness of some epidemic control measures, and more importantly, to offer a few tips on preventive measures.

negative: COVID-19 Information Seeking on Digital Media and Preventive Behaviors: The Mediation Role of Worry The high prevalence of novel coronavirus disease (COVID-19) and inefficient preventive measures taken to curb the disease are significant public health concerns. Rapid and innovative advances in digital media offer opportunities for health education, which could result in increased preventive behaviors. This study assessed preventive behaviors against contracting COVID-19 and tested mediation pathways linking four types of digital media consumption (social media, mobile social networking apps [MSNs], online news media, and social live steaming services [SLSSs]) to preventive behaviors, mediated by worry. Results from an online survey (N = 511) revealed that the vast majority (>90 percent) of respondents had very often or always practiced preventive behaviors against contracting COVID-19 such as washing their hands more regularly with soap and water, staying away from crowded places, and wearing face masks out in public. In addition, COVID-19 information seeking through the four types of digital media was a salient parameter that encouraged people to practice preventive behaviors either directly or indirectly. Specifically, seeking COVID-19-related information on MSNs, SLSSs, and online news media was directly associated with preventive behaviors. Whereas COVID-19 information consumption on social media, MSNs, and SLSSs during the infectious disease outbreak could elicit intense worry and, in turn, increase preventive behaviors. The reasons for and implications of the results are discussed.

negative: Antibiothérapie par voie générale en pratique courante dans les infections respiratoires basses de l'adulte et de l'enfant. Argumentaire

negative: The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65*109/L vs. 0.76*109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

negative: Chinese and Italian COVID-19 outbreaks can be correctly described by a modified SIRD model The COVID-19 disease is rapidly spreading in whole globe, affecting millions of people and pushing governments to take drastic measures to contain the outbreaks. The understanding of the dynamics of the epidemic is of great interest for the governments and health authorities that are facing COVID-19 outbreaks. The scarce presence of epidemiologic data, due to the still ongoing outbreaks, makes prediction difficult and mainly based on heuristic (fitting) models. However, these models with non-physical based parameters, can only give limited insight in the evolution of the outbreaks. In this work a SIRD compartmental model was developed to describe and predict the evolution of the Chinese and Italian outbreaks. Exploiting the similarities of the measures taken by the governments to contain the virus and of the total population number of Hubei province and Italy, the model was tuned on the Chinese outbreak (almost extinguished) and by perturbation the Italian outbreak was describe and predicted.

negative: Anti-SARS-CoV-2 hyperimmune plasma workflow Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus has become a Public Health Emergency of International Concern. Among the various treatment proposals for COVID-19 infection, passive immunotherapy using plasma from recovering patients - "convalescent plasma" (CP )- could be a promising option in the treatment of SARS-CoV-2 infections. Immune (i.e. "convalescent") plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. According to the World Health Organization (WHO), the use of plasma therapy is permitted when faced with «serious diseases for which there are no effective pharmacological treatments». Several clinical trials are underway to test the effectiveness of hyperimmune plasma at various stages of SARS-CoV2.The Food and Drug Administration (FDA), the U.S. regulatory authority, has approved the use of CP for compassionate use in the treatment of patients with a critical COVID-19 infection. Below are the general indications for drawing up clinical protocols for the integral management of "COVID-19-convalescent plasma" for which the validation and approval of the Ethics Committees is still necessary.

negative: COVID-19, SARS and MERS: A neurological perspective Abstract Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS, MERS and COVID-19. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.

negative: Diagnostic value and key features of computed tomography in Coronavirus Disease 2019 On 31 December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, China, and caused the outbreak of the Coronavirus Disease 2019 (COVID-19). To date, computed tomography (CT) findings have been recommended as major evidence for the clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the imaging characteristics and changes throughout the disease course in patients with COVID-19 in order to provide some help for clinicians. Typical CT findings included bilateral ground-glass opacity, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. This review also provides a comparison between COVID-19 and other diseases that have similar CT findings. Since most patients with COVID-19 infection share typical imaging features, radiological examinations have an irreplaceable role in screening, diagnosis and monitoring treatment effects in clinical practice.

negative: Therapeutic approach to respiratory infections in lung transplantation Abstract Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation.

negative: ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) is associated with adverse outcome in patients with cardiovascular disease (CVD). Aim To characterize the interaction between SARS-CoV-2 and Angiotensin Converting Enzyme 2 (ACE2) functional networks with focus on CVD. Methods Using bioinformatic tools, network medicine approaches and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction network which could be affected by SARS-CoV-2 infection. We identified top ACE2 interactors, including miRNAs which are shared regulators between the ACE2, virus-infection related proteins and heart interaction networks, using lung and nervous system networks as a reference. We also identified main SARS-CoV-2 risk groups and performed drug predictions for them. Results We found the same range of ACE2 expression confidence in respiratory and cardiovascular systems (averaging 4.48 and 4.64, respectively). Analysing the complete ACE2 interaction network, we identified 11 genes (ACE2, DPP4, ANPEP, CCL2, TFRC, MEP1A, ADAM17, FABP2, NPC1, CLEC4M, TMPRSS2) associated with virus-infection related processes. Previously described genes associated with cardiovascular risk factors DPP4, CCL2 and ANPEP were extensively connected with top regulators of ACE2 network, including ACE, INS and KNG1. Enrichment analysis revealed several disease phenotypes associated with interaction networks of ACE2, heart tissue, and virus-infection related protein, with the strongest associations with the following diseases (in decreasing rank order): obesity, hypertensive disease, non-insulin dependent diabetes mellitus, congestive heart failure, and coronary artery disease. We described for the first time microRNAs-miR (miR-302c-5p, miR-1305, miR-587, miR-26b-5p, and mir-27a-3p), which were common regulators of the three networks: ACE2, heart tissue and virus-infection related proteins. Conclusion Our study provides novel information regarding the complexity of signaling pathways affected by SARS-CoV-2 and proposes predictive tools as miR towards personalized diagnosis and therapy in COVID-19. Additionally, our study provides a list of miRNAs with biomarker potential in prediction of adverse outcome in patients with COVID-19 and CVD.

negative: Modeling COVID 19 in the Basque Country: from introduction to control measure response In March 2020, a multidisciplinary task force (so-called Basque Modelling Task Force, BMTF) was created to assist the Basque Health managers and the Basque Government during the COVID-19 responses. BMTF is a modeling team, working on different approaches, including statistical methods and artificial intelligence. In this paper we describe and present the results obtained by one of the modeling approaches developed within the BMTF, a stochastic SHARUCD-type models able to describe the disease incidence data, provided by the Basque Health Service, with a single parameter set. Data inspection has shown that the partial lockdown measures were effective to slowdown disease transmission in the Basque Country. Short and longer-term predictions are tested with good results adjusted to the current epidemiological data. The growth rate {lambda} is calculated from the model and from the data and the implications for the reproduction ratio r are shown. At the moment, the reproduction ratio r is estimated to be below the threshold behavior of r = 1, but still close to 1, meaning that although the number of new cases are decelerating, a careful monitoring of the development of the outbreak is required. Besides projections on the national health system needs during the increased population demand on hospital admissions, models were able to describe COVID-19 epidemic in the Basque Country, from introduction to control measure response and are now being used to monitor disease transmission when the country lockdown is gradually lifted. These are the first made public available modeling results for the Basque Country and the efforts will be continued taking into consideration the updated data and new information that are generated over time.

negative: Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics) The coronavirus disease (COVID-19) is highly pathogenic viral infection caused by SARS-CoV-2. Currently, COVID-19 has caused global health concern. It is assumed that COVID-19 has zoonotic origin based on the large number of infected people who were exposed to the wet market in Wuhan City, China. The phylogenetic analysis has revealed that SARS-CoV-2 has significant sequence similarity with severe acute respiratory syndrome-like (SARS-like) bat viruses, thus bats could be primary possible reservoir. The intermediate host and there subsequent transfer is not known yet, although human to human transfer is widely confirmed. The transmission of COVID-19 infection from one person to another resulted in the isolation of patients who were subsequently given a variety of treatments. To monitor the current outbreak, robust steps have been taken around the globe to reduce the transmission of COVID-19 infection particularly banning international and domestic flights, inducting lockdowns in vulnerable areas, social distancing etc. No clinically approved antiviral drug or vaccine against COVID-19 is reported yet. However, in clinical trials, few broad-spectrum antiviral drugs were evaluated against COVID-19 infection which resulted in clinical recovery. In this article emergence and pathogenicity of COVID-19 infection along with potential therapeutic strategies are analyzed to combat the COVID-19 pandemic.

negative: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.

negative: Key predictors of attending hospital with COVID19: An association study from the COVID Symptom Tracker App in 2,618,948 individuals Objectives: We aimed to identify key demographic risk factors for hospital attendance with COVID-19 infection. Design: Community survey Setting: The COVID Symptom Tracker mobile application co-developed by physicians and scientists at Kings College London, Massachusetts General Hospital, Boston and Zoe Global Limited was launched in the UK and US on 24th and 29th March 2020 respectively. It captured self-reported information related to COVID-19 symptoms and testing. Participants: 2,618,948 users of the COVID Symptom Tracker App. UK (95.7%) and US (4.3%) population. Data cut-off for this analysis was 21st April 2020. Main outcome measures: Visit to hospital and for those who attended hospital, the need for respiratory support in three subgroups (i) self-reported COVID-19 infection with classical symptoms (SR-COVID-19), (ii) self-reported positive COVID-19 test results (T-COVID-19), and (iii) imputed/predicted COVID-19 infection based on symptomatology (I-COVID-19). Multivariate logistic regressions for each outcome and each subgroup were adjusted for age and gender, with sensitivity analyses adjusted for comorbidities. Classical symptoms were defined as high fever and persistent cough for several days. Results: Older age and all comorbidities tested were found to be associated with increased odds of requiring hospital care for COVID-19. Obesity (BMI >30) predicted hospital care in all models, with odds ratios (OR) varying from 1.20 [1.11; 1.31] to 1.40 [1.23; 1.60] across population groups. Pre-existing lung disease and diabetes were consistently found to be associated with hospital visit with a maximum OR of 1.79 [1.64,1.95] and 1.72 [1.27; 2.31]) respectively. Findings were similar when assessing the need for respiratory support, for which age and male gender played an additional role. Conclusions: Being older, obese, diabetic or suffering from pre-existing lung, heart or renal disease placed participants at increased risk of visiting hospital with COVID-19. It is of utmost importance for governments and the scientific and medical communities to work together to find evidence-based means of protecting those deemed most vulnerable from COVID-19. Trial registration: The App Ethics have been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210

negative: Improved Chiral Separation of (R,S)-Goitrin by SFC: An Application in Traditional Chinese Medicine Like chemical drugs, research and development of herbal medicine also have a need to resolve enantiomers. To help illustrating the antiviral bioactivity of Isatidis Radix, a widely used traditional Chinese medicine (TCM), supercritical fluid chromatography (SFC) was used for analytical and preparative separation of (R,S)-goitrin, which was reported as the active ingredient of the herbal. Improved resolution was achieved on Chiralpak IC column, using acetonitrile as the organic modifier, representing a tenfold increase in speed, compared to the previous normal phase HPLC (NPLC) method. The newly developed chromatographic method was validated in terms of linearity, precision, limit of detection (LOD), and limit of quantitation (LOQ). Scale-up purification of (R)-goitrin and (S)-goitrin was performed on a preparative column with >90% total recovery. The absolute stereochemical assignment of the purified isomers was determined through optical rotation study. This attempt explored SFC's application in chiral research of traditional Chinese medicine.

negative: Lies, Gosh Darn Lies, and Not Enough Good Statistics: Why Epidemic Model Parameter Estimation Fails An opportunity exists in exploring epidemic modeling as a novel way to determine physiological and demic parameters for genetic association studies on a population/environmental (quasi) epidemiological study level. First, the spread of SARS-COV-2 has produced population specific lineages; second, epidemic spread model parameters are tied directly to these physiological and demic rates (e. g. incubation time, recovery time, transmission rate); and third, these parameters may serve as novel phenotypes to associate with region-specific genetic mutations as well as demic characteristics (e. g. age structure, cultural observance of personal space, crowdedness). Therefore, we sought to understand whether the parameters of epidemic models could be determined from the trajectory of infections, recovery, and hospitalizations prior to peak, and also to evaluate the quality and comparability of data between jurisdictions reporting their statistics necessary for the analysis of model parameters across populations. We found that, analytically, the pre-peak growth of an epidemic is limited by a subset of the model variates, and that the rate limiting variables are dominated by the expanding eigenmode of their equations. The variates quickly converge to the ratio of eigenvector components of the positive growth rate, which determines the doubling time. There are 9 parameters and 4 independent components in the eigenmode, leaving 5 undetermined parameters. Those parameters can be strikingly population dependent, and can have significant impact on estimates of hospital loads downstream. Without a sound framework, measurements of infection rates and other parameters are highly corrupted by uneven testing rates to uneven counting and reporting of relevant values. From the standpoint of phenotype parameters, this means that structured experiments must be performed to estimate these parameters in order to perform genetic association studies, or to construct viable models that accurately predict critical quantities such as hospitalization loads.

negative: Livestock infectious diseases and zoonoses. Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.

negative: COVID-19 and the cardiovascular system Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

negative: COVID-19 infection and recovery in various countries: Modeling the dynamics and evaluating the non-pharmaceutical mitigation scenarios The coronavirus disease 2019 (COVID-19) pandemic radically impacts our lives, while the transmission/infection and recovery dynamics of COVID-19 remain obscure. A time-dependent Susceptible, Exposed, Infectious, and Recovered (SEIR) model was proposed and applied to fit and then predict the time series of COVID-19 evolution observed in the last three months (till 3/22/2020) in various provinces and metropolises in China. The model results revealed the space dependent transmission/infection rate and the significant spatiotemporal variation in the recovery rate, likely due to the continuous improvement of screening techniques and public hospital systems, as well as full city lockdowns in China. The validated SEIR model was then applied to predict COVID-19 evolution in United States, Italy, Japan, and South Korea which have responded differently to monitoring and mitigating COVID-19 so far, although these predictions contain high uncertainty due to the intrinsic change of the maximum infected population and the infection/recovery rates within the different countries. In addition, a stochastic model based on the random walk particle tracking scheme, analogous to a mixing-limited bimolecular reaction model, was developed to evaluate non-pharmaceutical strategies to mitigate COVID-19 spread. Preliminary tests using the stochastic model showed that self-quarantine may not be as efficient as strict social distancing in slowing COVID-19 spread, if not all of the infected people can be promptly diagnosed and quarantined.

negative: The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources—Wikipedia, the GDELT Project and the Internet Archive—to quantify population-scale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geo-localized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical epidemic models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks.

negative: Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.

negative: The TVBG-SEIR spline model for analysis of COVID-19 spread, and a Tool for prediction scenarios Mathematical models are traditionally used to analyze the long-term global evolution of epidemics, to determine the potential and severity of an outbreak, and to provide critical information for identifying the type of disease interventions and intensity. One of the widely used mathematical models of long-term spreading of epidemics are the so-called deterministic compartmental models (SIR/SEIR type models). One of the main purposes of applying such models is to assess how the expensive restriction measures imposed by the authorities (home and social isolation/quarantine, travel restrictions, etc.) can effectively reduce the control reproduction number of the disease and its transmission risk. However the classical SIR/SEIR models have been primarily studied in what may be called stationary case, where the main parameters, the Transmission rate Beta (reflecting the virus spread by infected individuals) and the Removed rate Gamma (reflecting the hospitalization/isolation measures) remain constant during the whole period of interest. Hence, it is important to extend the classical SIR/SEIR models by creating new ansatzes for the dynamics of the transmission rates Beta(t) (which we will call further just Beta) and removed rates Gamma(t) (which we will call further just Gamma). The main purpose of the present research is to introduce a spline-based SEIR model with Time-varying Beta and Gamma parameters, or abbreviated TVBG-SEIR model, which is used to estimate the practical implications of the public health interventions and measures. We have designed a Tool based on the TVBG-SEIR model, which may be used as a Decision Support Tool to assist the health decision- and policy-makers in creating predictive scenarios.

negative: Machine Learning to Detect Self-Reporting of Symptoms, Testing Access, and Recovery Associated With COVID-19 on Twitter: Retrospective Big Data Infoveillance Study BACKGROUND: The coronavirus disease (COVID-19) pandemic is a global health emergency with over 6 million cases worldwide as of the beginning of June 2020. The pandemic is historic in scope and precedent given its emergence in an increasingly digital era. Importantly, there have been concerns about the accuracy of COVID-19 case counts due to issues such as lack of access to testing and difficulty in measuring recoveries. OBJECTIVE: The aims of this study were to detect and characterize user-generated conversations that could be associated with COVID-19-related symptoms, experiences with access to testing, and mentions of disease recovery using an unsupervised machine learning approach. METHODS: Tweets were collected from the Twitter public streaming application programming interface from March 3-20, 2020, filtered for general COVID-19-related keywords and then further filtered for terms that could be related to COVID-19 symptoms as self-reported by users. Tweets were analyzed using an unsupervised machine learning approach called the biterm topic model (BTM), where groups of tweets containing the same word-related themes were separated into topic clusters that included conversations about symptoms, testing, and recovery. Tweets in these clusters were then extracted and manually annotated for content analysis and assessed for their statistical and geographic characteristics. RESULTS: A total of 4,492,954 tweets were collected that contained terms that could be related to COVID-19 symptoms. After using BTM to identify relevant topic clusters and removing duplicate tweets, we identified a total of 3465 (<1%) tweets that included user-generated conversations about experiences that users associated with possible COVID-19 symptoms and other disease experiences. These tweets were grouped into five main categories including first- and secondhand reports of symptoms, symptom reporting concurrent with lack of testing, discussion of recovery, confirmation of negative COVID-19 diagnosis after receiving testing, and users recalling symptoms and questioning whether they might have been previously infected with COVID-19. The co-occurrence of tweets for these themes was statistically significant for users reporting symptoms with a lack of testing and with a discussion of recovery. A total of 63% (n=1112) of the geotagged tweets were located in the United States. CONCLUSIONS: This study used unsupervised machine learning for the purposes of characterizing self-reporting of symptoms, experiences with testing, and mentions of recovery related to COVID-19. Many users reported symptoms they thought were related to COVID-19, but they were not able to get tested to confirm their concerns. In the absence of testing availability and confirmation, accurate case estimations for this period of the outbreak may never be known. Future studies should continue to explore the utility of infoveillance approaches to estimate COVID-19 disease severity.

negative: Safety Guidelines for Sterility of Face Shields During COVID 19 Pandemic Face shields are personal protective equipment devices that are to be used by many health care workers during COVID 19 pandemic for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from droplet spread of infection. Face shields are generally not used alone, but in conjunction with other protective equipment like cap, mask, goggle, and are therefore classified as adjunctive personal protective equipment. In the wake of scarcity of face shields during the COVID 19 Pandemic, consideration of innovating newer methods of manufacturing must be considered to overcome the present day scarcity without jeopardising the safety of front line Heath care workers. All initial fast innovations comes with advantages and disadvantages, hence we thought of putting down simple guidelines for new emerged face shield use.

negative: Deep Impact of COVID-19 in the HealthCare of Latin America: the case of Brazil

negative: Clinical and behavioural characteristics of self-isolating healthcare workers during the COVID-19 pandemic: a single-centre observational study Objectives:To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19. Design: A cross-sectional, single-centre study. Setting: A large, teaching hospital based in Central London with tertiary infection services. Participants: 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were female and 65 male. Measures: Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report. Results: The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020. Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off. Conclusion: There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Conclusions cannot be drawn about exact numbers of confirmed cases due to lack of diagnostic swabbing. There were significant numbers of respondents reporting anosmia; as well as early non-specific illness prior to onset of cough and fever. This may represent pre-symptomatic HCWs who are likely to be infectious and thus criteria for isolation and swabbing should be broadened. The study also revealed concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This should be addressed urgently to reduce risk of severe disease being detected late. Finally, this study should inform trusts that HCWs may require longer than 7 days off work to recover from illness.

negative: Novel Coronavirus COVID-19 Strike on Arab Countries and Territories: A Situation Report I The novel Coronavirus (COVID-19) is an infectious disease caused by a new virus called COVID-19 or 2019-nCoV that first identified in Wuhan, China. The disease causes respiratory illness (such as the flu) with other symptoms such as a cough, fever, and in more severe cases, difficulty breathing. This new Coronavirus seems to be very infectious and has spread quickly and globally. In this work, information about COVID-19 is provided and the situation in Arab countries and territories regarding the COVID-19 strike is presented. The next few weeks main expectations is also given.

negative: Involvement of the Nervous System in SARS-CoV-2 Infection As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.

negative: Novel Coronavirus Infection in Newborn Babies Under 28 Days in China Previous studies described the clinical features of Covid-19 in adults and infants under 1 year of age. Little is known about features, outcomes and intrauterine transmission potential in newborn babies aged 28 days or less. Through systematical searching, we identified 4 infections in newborn babies in China as of March 13. The age range was 30 h to 17 days old. Three were male. Two newborn babies had fever, 1 had shortness of breath, 1 had cough and 1 had no syndromes. Supportive treatment was provided for all 4 newborn babies. None required intensive unit care or mechanical ventilation. None had any severe complications. Three newborn babies recovered by the end of this study and had been discharged with 16, 23, and 30 days of hospital stay. All 4 mothers were infected by SARS-CoV-2, 3 showing symptoms before and 1 after delivery. Cesarean section was used for all 4 mothers, 3 at level III hospitals and 1 at a level II hospital. Three newborn babies were separated from mothers right after being born and were not breastfed. In summary, newborn babies are susceptible to SARS-CoV-2 infection. The symptoms in newborn babies were milder and outcomes were less severe as compared to adults. Intrauterine vertical transmission is possible but direct evidence is still lacking.

negative: Awareness, Attitudes, and Actions Related to COVID-19 Among Adults With Chronic Conditions at the Onset of the U.S. Outbreak: A Cross-sectional Survey BACKGROUND: The evolving outbreak of coronavirus disease 2019 (COVID-19) is requiring social distancing and other measures to protect public health. However, messaging has been inconsistent and unclear. OBJECTIVE: To determine COVID-19 awareness, knowledge, attitudes, and related behaviors among U.S. adults who are more vulnerable to complications of infection because of age and comorbid conditions. DESIGN: Cross-sectional survey linked to 3 active clinical trials and 1 cohort study. SETTING: 5 academic internal medicine practices and 2 federally qualified health centers. PATIENTS: 630 adults aged 23 to 88 years living with 1 or more chronic conditions. MEASUREMENTS: Self-reported knowledge, attitudes, and behaviors related to COVID-19. RESULTS: A fourth (24.6%) of participants were “very worried” about getting the coronavirus. Nearly a third could not correctly identify symptoms (28.3%) or ways to prevent infection (30.2%). One in 4 adults (24.6%) believed that they were “not at all likely” to get the virus, and 21.9% reported that COVID-19 had little or no effect on their daily routine. One in 10 respondents was very confident that the federal government could prevent a nationwide outbreak. In multivariable analyses, participants who were black, were living below the poverty level, and had low health literacy were more likely to be less worried about COVID-19, to not believe that they would become infected, and to feel less prepared for an outbreak. Those with low health literacy had greater confidence in the federal government response. LIMITATION: Cross-sectional study of adults with underlying health conditions in 1 city during the initial week of the COVID-19 U.S. outbreak. CONCLUSION: Many adults with comorbid conditions lacked critical knowledge about COVID-19 and, despite concern, were not changing routines or plans. Noted disparities suggest that greater public health efforts may be needed to mobilize the most vulnerable communities. PRIMARY FUNDING SOURCE: National Institutes of Health.

negative: An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI) Background: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. Methods: Our study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. Findings: This study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical(P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. Conclusions: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care.

negative: Associations of clinical characteristics and antiviral drugs with viral RNA clearance in patients with COVID-19 in Guangzhou, China: a retrospective cohort study Background: The novel coronavirus disease 2019 (COVID-19) characterized by respiratory symptoms has become a global pandemic although factors influencing viral RNA clearance remained unclear to inform optimal isolation period and treatment strategies. Methods: In this retrospective study, we included patients with confirmed COVID-19 admitted to Guangzhou Eighth People's Hospital from 20th January 2020 to 15th March 2020. The associations of clinical characteristics and treatment regimens on time to viral RNA clearance were analyzed. Results: We examined 284 consecutive COVID-19 cases, accounting for 82% of confirmed cases in Guangzhou during this period. At the time of reporting (20th March 2020), 276 (97.2%) had recovered and were discharged from hospital with a median hospital stay of 18 days (interquartile range [IQR]:13-24). Overall, 280 patients achieved viral RNA clearance with a median length of 12 days (IQR: 8-16) after onset of illness. Amongst them, 66.1% had viral RNA cleared within 14 days, and 89.3% within 21 days. Older age, severity of disease, time lag from illness onset to hospital admission, high body temperature, and corticosteroid use were associated with delayed clearance of viral RNA. None of the antiviral regimens (chloroquine, oseltamivir, arbidol, and lopinavir/ritonavir) improved viral RNA clearance. The use of lopinavir/ritonavir was associated with delayed clearance of viral RNA even after adjusting for confounders. Conclusion: In patients with COVID-19, isolation for a minimum of 21 days after onset of illness may be warranted, while the use of antiviral drugs does not enhance viral RNA clearance.

negative: COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Abstract Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2–14 days, and mostly 3–7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.

negative: A new threat from an old enemy: Re-emergence of coronavirus (Review) The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. In the present review, we address current knowledge on coronaviruses from a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies. Although a great amount of research and efforts have been made worldwide to prevent further outbreaks of coronavirus-associated disease, the spread and lethality of the 2019 outbreak (COVID-19) is proving to be higher than previous epidemics on account of international travel density and immune naivety of the population. Only strong, joint and coordinated efforts of worldwide healthcare systems, researchers, and pharmaceutical companies and receptive national leaders will succeed in suppressing an outbreak of this scale.

negative: Hochsicherheitslabor Das Planen, Bauen und Betreiben eines Hochsicherheitslabors muss sehr gut vorbereitet werden. Nutzer, spätere Anlagenbetreiber (Technik und Bau) und die Genehmigungsbehörde sollten rechtzeitig in das Verfahren eingebunden werden. Umfangreiche technische Kenntnisse, insbesondere das Zusammenspiel gewerksübergreifender Funktionen, sind notwendig. Dabei steht die Sicherheit an oberster Stelle. Dieses Kapitel gibt einen fundierten Überblick über die rechtlichen Grundlagen und Sicherheitsaspekte, die bei der Planung, der Errichtung und dem Betrieb von Hochsicherheitslaboren beachtet werden müssen.

negative: [Tracheal intubation in patients with severe and critical COVID-19: analysis of 18 cases]. OBJECTIVE To analyze the clinical characteristics of patients with severe or critical coronavirus disease 2019 (COVID-19) receiving tracheal intubation. METHODS We analyzed clinical characteristics of 18 severely or critically ill patients with COVID-19 undergoing tracheal intubation. The general demographic and clinical data of the patients including their age, gender, pre- intubation state of consciousness and the ventilation mode were recorded. The anesthesiologists performing the tracheal intubation procedure evaluated and recorded the tracheal intubation conditions of the patients. The changes in the vital signs of the patients before anesthesia induction and after intubation were recorded. RESULTS The average ages of these patients were 70.39±8.02 years. Fifteen patients (83.33%) received non- invasive ventilation before tracheal intubation, and 13 patients (72.22%) were conscious before tracheal intubation. After induction of anesthesia, the blood pressure and heart rate of the patients decreased significantly (P < 0.05). Most of the patients (94.44%) were in excellent or good conditions for tracheal intubation, and the first-attempt success rate of tracheal intubation was 100%. Five patients died within 3 weeks following the intubation. Tracheotomy was performed in one patient. Twelve patients were still on endotracheal mechanical ventilation in the intensive care unit, and one of them received ECMO treatment due to poor oxygenation. A total of 16 experienced anesthesiologists participated in tracheal intubation, all with third-level protection during the operation, and no medical staff infection has been detected so far. CONCLUSIONS For patients with severe and critical COVID-19 and indications of tracheal intubation, we recommend early intubation with invasive respiratory support to improve the treatment efficacy and reduce the mortality. Anesthetic agents should be used carefully during tracheal intubation to ensure patients' safety. The medical staff should have a high-level protection during the intubation to maximally ensure their safety.

negative: [Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19]. Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

negative: Child with liver transplant recovers from COVID-19 infection. A case report We present the case of a 55-month-old girl who recovered from coronavirus disease 2019 (COVID-19) infection 5 months after undergoing liver transplantation; she had a co-infection with Epstein-Barr virus (EBV). To the best of our knowledge, this is the first case report of a COVID-19 infection in a pediatric patient with liver transplantation. Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.

negative: Dynamics of the COVID-19 pandemic in India Understanding the dynamics of the COVID-19 pandemic is crucial for improved control and social distancing strategies. To that effect, we have employed the susceptible-exposed-infectious-recovered model, refined by contact tracing and hospitalization data from Indian provinces Kerala, Delhi, Maharashtra, and West Bengal, as well as from overall India. We have performed a sensitivity analysis to identify the most crucial input parameters, and we have calibrated the model to describe the data as best as possible. Short-term predictions reveal an increasing and worrying trend of COVID-19 cases for all four provinces and India as a whole, while long-term predictions also reveal the possibility of oscillatory dynamics. Our research thus leaves the option open that COVID-19 might become a seasonal occurrence. We also simulate and discuss the impact of media on the dynamics of the COVID-19 pandemic.

negative: Association of Cardiovascular Manifestations with In-hospital Outcomes in Patients with COVID-19: A Hospital Staff Data Background: The outbreaks of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain a huge threat to the public health worldwide. Clinical data is limited up to now regarding the risk factors in favor of severe conversion of non-severe case with COVID-19. Aims: This study analyzed a hospital staff data to figure out general clinical features of COVID-19 in terms of the association of cardiovascular manifestations (CVMs) with in-hospital outcomes of COVID-19 cases. Methods: Retrospective, single-center case series of 41 consecutive hospitalized health staff with confirmed COVID-19 were collected at the Central Hospital of Wuhan in Wuhan, China, from January 15 to January 24, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment data and in-hospital adverse events were collected and analyzed. Final date of follow-up was March 3, 2020. A comparative study was applied between cases with CVMs and those without CVMs. Results: Of all, clinicians and clinical nurses accounted for 80.5%, while 87.8% of all had history of patient contact. The population was presented with a mean age of 39.1 +- 9.2 and less comorbidities than community population. The three most frequent symptoms of COVID-19 cases analyzed were fever (82.9%), myalgia or fatigue (80.5%) and cough (63.4%). While, the three most frequent initial symptoms were myalgia or fatigue (80.5%), fever (73.2%) and cough (41.5%). There were 95.1% cases featured as non-severe course of disease according to the official standard in China. Patients with CVMs and those without CVMs accounted for 58.5% and 41.5%, respectively. Compared with cases without CVMs, patients with CVMs were presented with lower baseline lymphocyte count (0.99 +- 0.43 and 1.55 +- 0.61, P<0.001), more who had at least once positive nucleic acid detection of throat swab during admission (50.0% and 11.8%, P=0.011), and more received oxygen support (79.2% and 23.5%, P<0.001). The rate of in-hospital adverse events was significantly higher in patients with CVMs group (75.0% and 23.5%, P=0.001). Multivariable logistic regression model indicated that, coexisting with CVMs in COVID-19 patients was not independently associated with in-hospital adverse events. Conclusions: Most of hospital staff with COVID-19 had history of patient contact, featured non-severe course of disease. Cases with CVMs suffered from more in-hospital adverse events than those without CVMs. But concomitant CVMs were not independently associated with in-hospital adverse events in COVID-19 patients.

negative: Managing the supportive care needs of those affected by COVID-19 Globally, the number of people affected by coronavirus disease 2019 (COVID-19) is rapidly increasing. In most (>80%), the illness is relatively mild and can be self-managed out of hospital. However, in about 20% the illness causes respiratory compromise severe enough to require hospital admission [1]. Patients with severe and critical disease need full active treatment. This may include oxygen for hypoxaemia and ventilatory support, along with optimal management of complications, e.g. super-imposed bacterial infection, and any underlying co-morbidities, e.g. chronic obstructive pulmonary disease, congestive heart failure. To date, no antiviral agent has shown to be effective in treating the disease [2].

negative: The COVID-19 containment in Vietnam: What are we doing?

negative: Psychological Intervention and COVID-19: What We Know So Far and What We Can Do The coronavirus COVID-19 and the global pandemic has already had a substantial disruptive impact on society, posing major challenges to the provision of mental health services in a time of crisis, and carrying the spectre of an increased burden to mental health, both in terms of existing psychiatric disorder, and emerging psychological distress from the pandemic. In this paper we provide a framework for understanding the key challenges for psychologically informed mental health care during and beyond the pandemic. We identify three groups that can benefit from psychological approaches to mental health, and/or interventions relating to COVID-19. These are (i) healthcare workers engaged in frontline response to the pandemic and their patients; (ii) individuals who will experience the emergence of new mental health distress as a function of being diagnosed with COVID-19, or losing family and loved ones to the illness, or the psychological effects of prolonged social distancing; and (iii) individuals with existing mental health conditions who are either diagnosed with COVID-19 or whose experience of social distancing exacerbates existing vulnerabilities. Drawing on existing literature and our own experience of adapting treatments to the crisis we suggest a number of salient points to consider in identifying risks and offering support to all three groups. We also offer a number of practical and technical considerations for working psychotherapeutically with existing patients where COVID-19 restrictions have forced a move to online or technologically mediated delivery of psychological interventions.

negative: Progression, recovery and fatality in patients with SARS-CoV-2 related pneumonia in Wuhan, China: a single-centered, retrospective, observational study Objectives To determine the case fatality rates and death risk factors. Design Retrospective case series. Setting A COVID-19 ward of a secondary Hospital in Wuhan, China. Participants Consecutively hospitalized COVID-19 patients between Jan 3, 2020 and Feb 27, 2020. Outcomes were followed up to discharge or death. Results Of 121 patients included, 66 (54.6%) were males. The median age was 59 (IQR: 46 to 67) years, and hypertension (33 patients; 27.3%) the leading comorbidity. Lymphopenia (83 of 115 patients; 72.2%) frequently occurred and then normalized on day 4 (IQR: 3 to 6) after admission in the survivors, with lung lesion absorbed gradually on day 8 (IQR: 6 to10) after onset (33 of 57 patients; 57.9%). The real-time polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 were positive in 78 (78/108; 72.2%) patients, and a false-negative RT-PCR occurred in 15 (13.9%) patients. Hypoxemia occurred in 94 (94/117; 80.3%) patients, and supplemental oxygen was given in 88 (72.7%) patients, and mon-invasive or invasive ventilation in 20 (16.5%) cases. Corticosteroid use might link to death. The case fatality rates were 4.4% (one of 23 patients), 29.3% (12/41), 22.8% (13/57) or 45% (9/20) for patients with moderate, severe, critical illness or on ventilator. The length of hospital stay was 14 (IQR: 10 to 20) days, and selfcare ability worsened in 21 patients (21/66; 31.8%) cases. Patients over 60 years were most likely to have poorer outcomes, and increasing in age by one-year increased risk for death by 18% (CI: 1.04-1.32). Conclusions In management of patients with SARS-CoV-2 pneumonia, especially the elderly with hypertension, close monitoring and appropriate supportive treatment should be taken earlier and aggressively to prevent from developing severe or critical illness. Corticosteroid use might link to death. Repeated RT-PCR tests or novel detection methods for SARS-CoV-2 should be adopted to improve diagnostic efficiency.

negative: Pharmacotherapy in COVID-19; A narrative review for emergency providers INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords “COVID 19,” “SARS-CoV-2,” and “treatment.” All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Glucocorticoids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.

negative: Need for ensuring care for neuro-emergencies—lessons learned from the COVID-19 pandemic BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

negative: Likelihood of survival of coronavirus disease 2019

negative: Mathematical Modeling of Epidemic Diseases; A Case Study of the COVID-19 Coronavirus The outbreak of the Coronavirus COVID-19 has taken the lives of several thousands worldwide and locked-out many countries and regions, with yet unpredictable global consequences. In this research we study the epidemic patterns of this virus, from a mathematical modeling perspective. The study is based on an extensions of the well-known susceptible-infected-recovered (SIR) family of compartmental models. It is shown how social measures such as distancing, regional lockdowns, quarantine and global public health vigilance, influence the model parameters, which can eventually change the mortality rates and active contaminated cases over time, in the real world. As with all mathematical models, the predictive ability of the model is limited by the accuracy of the available data and to the so-called level of abstraction used for modeling the problem. In order to provide the broader audience of researchers a better understanding of spreading patterns of epidemic diseases, a short introduction on biological systems modeling is also presented and the Matlab source codes for the simulations are provided online.

negative: Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Method: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than 27 mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19. Conclusion: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.

negative: Operational protocol for donation of anti‐COVID‐19 convalescent plasma in Italy Coronavirus Disease 19 (COVID-19) represents a public health threat worldwide and Italy at the present time is considered the epicenter of this severe infection in the western world. Unfortunately, no standardized therapy does exist for COVID-19 and a number of investigational drugs for use in patients with life-threatening COVID-19 infections have been tried. One investigational treatment being explored for COVID-19 involves the use of convalescent plasma collected from recovered COVID-19 patients.

negative: Poor-sleep is associated with slow recovery from lymphopenia and an increased need for ICU care in hospitalized patients with COVID-19: A retrospective cohort study Sleep is known to play an important role in immune function. However, the effects of sleep quality during hospitalization for COVID-19 remain unclear. This retrospective, single-center cohort study was conducted to investigate the effects of sleep quality on recovery from lymphopenia and clinical outcomes in hospitalized patients with laboratory-confirmed COVID-19 admitted to the West District of Wuhan Union Hospital between January 25 and March 15, 2020. The Richards-Campbell sleep questionnaire (RCSQ) and Pittsburgh Sleep Quality Index (PSQI) were used to assess sleep quality. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected from electronic medical records and compared between the good-sleep group and poor-sleep group. In all, 135 patients (60 in good-sleep group and 75 in poor-sleep group) were included in this study. There were no significant between-group differences regarding demographic and baseline characteristics, as well as laboratory parameters upon admission and in-hospital treatment. Compared with patients in the good-sleep group, patients in the poor-sleep group had lower absolute lymphocyte count (ALC) (day 14: median, 1.10 vs 1.32, P = 0.0055; day 21: median, 1.18 vs 1.48, P = 0.0034) and its reduced recovery rate (day 14: median, 56.91 vs 69.40, P = 0.0255; day 21: median, 61.40 vs 111.47, P = 0.0003), as well as increased neutrophil-to-lymphocyte ratio (NLR; day 14: median, 3.17 vs 2.44, P = 0.0284; day 21: median, 2.73 vs 2.23, P = 0.0092) and its associated deterioration rate (day 14: median, -39.65 vs -61.09, P = 0.0155; day 21: median, -51.40% vs -75.43, P = 0.0003). Nine [12.0%] patients in the poor-sleep group required ICU care (P = 0.0151); meanwhile, none of the patients in good-sleep group required ICU care. Patients in the poor-sleep group had increased duration of hospital stay (33.0 [23.0–47.0] days vs 25.0 [20.5–36.5] days, P = 0.0116) compared to those in the good-sleep group. An increased incidence of hospital-acquired infection (seven [9.3%] vs one [1.7%]) was observed in the poor-sleep group compared to the good-sleep group; however, this difference was not significant (P = 0.1316). In conclusion, poor sleep quality during hospitalization in COVID-19 patients with lymphopenia is associated with a slow recovery from lymphopenia and an increased need for ICU care.

negative: Complications des tatouages : classification clinique, histologique, physiopathologique, cinétique des particules Résumé Les tatouages sont de plus en plus fréquents et leur surface est en augmentation. Ils sont également de plus en plus colorés. Les complications sont fréquentes et réalisent des tableaux cliniques et histologiques très variés. Les encres, dont la composition n’est pas toujours connue, contiennent de nombreux pigments dont les produits de dégradation peuvent entraîner des allergies chroniques. Les effets à long terme de la présence de produits carcinogènes et de nanoparticules justifient la réalisation d’études prospectives. Le public devrait être informé de ces complications et des difficultés du détatouage. Summary Tattoos are more and more frequent and their surface is increasing. They are also becoming more and more colorful. Complications are frequent and induce a wide variety of clinical and histological pictures. The inks, the composition of which is not always known, contain many pigments which degradation products can lead to chronic allergies. The long-term effects of the presence of carcinogenic products and nanoparticles justify the carrying out of prospective studies. The public should be made aware of these complications and of the difficulties of tattoo removal.

negative: Thousands of people will help scientists to track the long-term health effects of the coronavirus crisis

negative: The effects of glass surfaces and probe GC content on signal intensities of a 60-mer diagnostic microarray The effects of glass surfaces and probe GC content on signal intensities of a 60-mer diagnostic microarray were studied. Twelve virus-specific oligonucleotide probes for severe acute respiratory syndrome coronavirus (SARS-CoV) were divided into a high GC content group (≥ 50%) and a low GC content group (< 50%), and spotted onto four different chemically-modified glass surfaces: a poly-amine coating activated by 1,4-phenylene diisothiocyanate (Poly-Amine surface), an acrylic acid-co-acrylamide copolymer coating activated by 1-(3-dimethylamino propyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (AACA-Copolymer surface), a commercial Corning CMT-GAPS amino surface, and a Telechem SuperAmine amino surface. RNA samples from cultured SARS-CoV strain were labelled using direct cDNA labelling with restriction display in a single colour format. The background-subtracted signal intensities were analysed using two-way analysis of variance. The effects of glass surfaces on background-subtracted signal intensities were significant (p=0.003). Multiple comparisons showed that differences existed mainly between the AACA-Copolymer surface and the other glass surfaces, and that the AACA-Copolymer surface had the highest background-subtracted signal intensity. The probe GC content had no significant effect on signal intensities in the narrow range of GC content represented (p=0.07). The results suggested that the AACA-Copolymer surface may be a novel choice of microorganism survey based on long oligonucleotide microarray.

negative: The enemy who sealed the world: Effects quarantine due to the COVID-19 on sleep quality, anxiety, and psychological distress in the Italian population BACKGROUND: The 2019 Coronavirus Disease (COVID-19) pandemic has become a global health emergency. The extreme actions aimed to reduce virus diffusion have profoundly changed the lifestyles of the Italian population. Moreover, fear of contracting the infection has generated high levels of anxiety. This study aimed to understand the psychological impact of the COVID-19 outbreak on sleep quality, general anxiety symptomatology, and psychological distress. METHODS: An online survey collected information on socio-demographic data and additional information concerning the COVID-19 pandemic. Furthermore, sleep quality, sleep disorders, generalized anxiety symptoms, psychological distress, and post-traumatic stress disorder (PTSD) symptomatology related to COVID-19 were assessed. RESULTS: This study included 2291 respondents. The results revealed that 57.1% of participants reported poor sleep quality, 32.1% high anxiety, 41.8% high distress, and 7.6% reported PTSD symptomatology linked to COVID-19. Youth and women, those uncertain regarding possible COVID-19 infection, and greater fear of direct contact with those infected by COVID-19 had an increased risk of developing sleep disturbances, as well as higher levels of anxiety and distress. Finally, a significant relationship between sleep quality, generalized anxiety, and psychological distress with PTSD symptoms related to COVID-19 was evidenced. CONCLUSIONS: Our findings indicate that the COVID-19 pandemic appears to be a risk factor for sleep disorders and psychological diseases in the Italian population, as previously reported in China. These results should be used as a starting point for further studies aimed to develop psychological interventions to minimize the brief and long-term consequences of the COVID-19 pandemic.

negative: Compliance with the ERAS Protocol and 3-Year Survival After Laparoscopic Surgery for Non-metastatic Colorectal Cancer. INTRODUCTION Enhanced recovery after surgery (ERAS) pathways have been proven to enhance postoperative recovery, reduce morbidity, and reduce length of hospital stay after colorectal cancer surgery. However, despite the benefits of the ERAS program on short-term results, little is known about its impact on long-term results. OBJECTIVE The aim of the study was to determine the association between adherence to the ERAS protocol and long-term survival after laparoscopic colorectal resection for non-metastatic cancer. MATERIAL AND METHODOLOGY Between 2013 and 2016, 350 patients underwent laparoscopic colorectal cancer resection in the 2nd Department of General Surgery, Jagiellonian University Medical College, and were enrolled for further analysis. The relationship between the rate of compliance with the ERAS protocol and 3-year survival was analyzed according to the Kaplan-Meier method with log-rank tests. Patients were divided into two groups according to their degree of adherence to the ERAS interventions: Group 1 (109 patients), < 80% adherence, and Group 2 (241 patients), ≥ 80% adherence. The primary outcome was overall 3-year survival. The secondary outcomes were postoperative complications, length of hospital stay, and recovery parameters. RESULTS The groups were similar in terms of demographics and surgical parameters. The median compliance to ERAS interventions was 85.2%. The Cox proportional model showed that AJCC III (HR 3.28, 95% CI 1.61-6.59, p = 0.0021), postoperative complications (HR 2.63, 95% CI 1.19-5.52, p = 0.0161), and compliance with ERAS protocol < 80% (HR 3.38, 95% CI 2.23-5.21, p = 0.0102) were independent predictors for poor prognosis. Additionally, analysis revealed that adherence to the ERAS protocol in Group 2 with ≥ 80% adherence was associated with a significantly shorter length of hospital stay (6 vs. 4 days, p < 0.0001), a lower rate of postoperative complications (44.7% vs. 23.3%, p < 0.0001), and improved functional recovery parameters: tolerance of oral diet (53.4% vs. 81.5%, p < 0.0001) and mobilization (77.7% vs. 96.1%, p < 0.0001) on the first postoperative day. CONCLUSIONS AND RELEVANCE This study reports an association between adherence to the ERAS protocol and long-term survival after laparoscopic colorectal resection for non-metastatic cancer. Lower adherence to the protocol, independent from stage of cancer and postoperative complications, was an independent risk factors for poorer survival rates.

negative: COVID-19 and Advanced Practice Registered Nurses (APRNs): Frontline update #1 COVID-19 emerged in 2019 and rapidly became a global pandemic infecting millions, killing hundreds of thousands. The disease altered the practices of hospitals, clinics, and patients. These changes have implications for Advanced Practice Registered Nurses (APRNs). APRNs must remain current on best practices for treatment and diagnosis of COVID-19 while being cognizant of changes to their scope of practice. As the pandemic continues, APRNs will remain on the front lines treating COVID-19 patients while also caring for vulnerable populations within the community. To provide high-quality care, APRNs must utilize a multi-faceted approach that heeds ongoing updates to evidence-based practice.

negative: Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus. Severe acute respiratory syndrome with high mortality rates (~50%) is associated with a novel group 2c betacoronavirus designated Middle East respiratory syndrome coronavirus (MERS-CoV). We synthesized a panel of contiguous cDNAs that spanned the entire genome. Following contig assembly into genome-length cDNA, transfected full-length transcripts recovered several recombinant viruses (rMERS-CoV) that contained the expected marker mutations inserted into the component clones. Because the wild-type MERS-CoV contains a tissue culture-adapted T1015N mutation in the S glycoprotein, rMERS-CoV replicated ~0.5 log less efficiently than wild-type virus. In addition, we ablated expression of the accessory protein ORF5 (rMERS•ORF5) and replaced it with tomato red fluorescent protein (rMERS-RFP) or deleted the entire ORF3, 4, and 5 accessory cluster (rMERS-ΔORF3-5). Recombinant rMERS-CoV, rMERS-CoV•ORF5, and MERS-CoV-RFP replicated to high titers, whereas MERS-ΔORF3-5 showed 1-1.5 logs reduced titer compared with rMERS-CoV. Northern blot analyses confirmed the associated molecular changes in the recombinant viruses, and sequence analysis demonstrated that RFP was expressed from the appropriate consensus sequence AACGAA. We further show dipeptidyl peptidase 4 expression, MERS-CoV replication, and RNA and protein synthesis in human airway epithelial cell cultures, primary lung fibroblasts, primary lung microvascular endothelial cells, and primary alveolar type II pneumocytes, demonstrating a much broader tissue tropism than severe acute respiratory syndrome coronavirus. The availability of a MERS-CoV molecular clone, as well as recombinant viruses expressing indicator proteins, will allow for high-throughput testing of therapeutic compounds and provide a genetic platform for studying gene function and the rational design of live virus vaccines.

negative: Novel coronavirus (2019-nCoV): Update on 3rd Coronavirus Outbreak of 21st Century

negative: Population based estimates of comorbidities affecting risk for complications from COVID-19 in the US We used 2017 Behavioral Risk Factor Surveillance System (BRFSS) data (N=444,649) to estimate the proportion of US adults who report comorbidities that suggest heightened risk of complications from COVID-19. Co-morbidities included cardiovascular disease, chronic obstructive pulmonary disease (COPD), diabetes, asthma, hypertension, and/or cancer other than skin, based on data from China. Overall 45.4% (95% CI 45.1-45.7) of adults reported any of the 6 comorbidities, increasing from 19.8% (19.1-20.4) for ages 18-29 years to 80.7% (79.5-81.8) for ages 80+ years. State rates ranged from 37.3% (36.2-38.5) in Utah to 58.7% (57.0-60.4) in West Virginia. Rates also varied by race/ethnicity, health insurance status, and employment. Excluded were residents of nursing homes or assisted living facilities. Although almost certainly an underestimate of all adults at risk due to these exclusions, these results should help in estimating healthcare needs for adults with COVID-19 complications living in the community.

negative: Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia INTRODUCTION: The purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia. METHODS: A retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups. RESULTS: Twenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up. CONCLUSIONS: This ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.

negative: Covid-19 Crisis Triage - Optimizing Health Outcomes and Disability Rights.

negative: Pulmonary sequelae in a patient recovered from swine flu The pandemic of swine flu (H1N1) influenza spread to involve the whole world rapidly. Many patients manifested a mild clinical illness but some developed pneumonia and respiratory failure. High mortality was observed in patients with severe disease. Among survivors, studies are limited. Ground-glass opacities on a high-resolution computerized tomography scan and reduced diffusion capacity were noted after 3 months in a study. But long-term complications in patients with swine flu pneumonia have not been studied well. We are presenting an unusual case of swine flu pneumonia who developed interstitial lung disease after recovery.

negative: Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2 OBJECTIVE: To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. STUDY DESIGN: This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). RESULTS: Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. CONCLUSION: Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. KEY POINTS: · Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth.. · Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth.. · Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed..

negative: Assessing the Impact of COVID-19 on the Objective and Analysis of Oncology Clinical Trials -- Application of the Estimand Framework COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related intercurrent events, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for.

negative: Current targeted therapeutics against COVID-19: based on first-line experience in china Abstract SARS-CoV-2 is a novel strain, causing a global pandemic since the end of 2019. The majority of patients showed nonspecific symptoms such as fever, dry cough, and fatigue. Most patients have a good prognosis while some with severe conditions could rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and even die. The exacerbation of the patient's condition may be due to a cytokine storm in the body. Effective targeted therapies including antiviral and immunization are urgently needed. Although many clinical trials are already underway and the majority of patients have received antiviral therapy based on medication experience with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and preliminary results from some clinical trials, there are no antiviral drugs proven to be effective currently. We summarize the current therapeutic medicines used in the clinic, hope to be able to provide some implications for clinical medication.

negative: Kidney impairment is associated with in-hospital death of COVID-19 patients Background: Information on kidney impairment in patients with coronavirus disease 2019 (COVID-19) is limited. This study aims to assess the prevalence and impact of abnormal urine analysis and kidney dysfunction in hospitalized COVID-19 patients in Wuhan. Method: We conducted a consecutive cohort study of COVID-19 patients admitted in a tertiary teaching hospital with 3 branches following a major outbreak in Wuhan in 2020. Hematuria, proteinuria, serum creatinine concentration and other clinical parameters were extracted from the electronic hospitalization databases and laboratory databases. Incidence rate for acute kidney injury (AKI) was examined during the study period. Association between kidney impairment and in-hospital death was analyzed. Results: We included 710 consecutive COVID19 patients, 89 (12.3%) of whom died in hospital. The median age of the patients was 63 years (inter quartile range, 51-71), including 374 men and 336 women. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. Conclusion: The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. Clinicians should increase their awareness of kidney impairment in hospitalized COVID-19 patients.

negative: A Critical Appraisal of COVID-19 in Malaysia and Beyond When the first report of COVID-19 appeared in December 2019 from Wuhan, China, the world unknowingly perceived this as another flu-like illness. Many were surprised at the extreme steps that China had subsequently taken to seal Wuhan from the rest of the world. However, by February 2020, the SARS-CoV-2 virus, which causes COVID-19, had spread so quickly across the globe that the World Health Organization officially declared COVID-19 a pandemic. COVID-19 is not the first pandemic the world has seen, so what makes it so unique in Malaysia, is discussed to avoid a future coronacoma.

negative: Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018 BACKGROUND: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir. AIM: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2). DESIGN AND SETTING: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries. METHOD: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache. RESULTS: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3–6) versus 5 days (IQR 3–8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; P = 0.026). CONCLUSION: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19.

negative: Covid-19 and long term conditions: what if you have cancer, diabetes, or chronic kidney disease?

negative: Global coronavirus disease 2019: what has daily cumulative index taught us? ABSTRACT In addition to the absolute case number, a rapid increase in the number of COVID-19 cases within a short time was supposed to result in insufficiency of the healthcare system and further negatively affect patients’ outcomes. This study was conducted to investigate the association between the outcomes of COVID-19 patients and daily cumulative index (DCI), which was defined as the average daily number of new cases of COVID-19 and calculated by cumulative cases/number of days between the first reported case and March 6, 2020 by country. Spearman's rank correlation analyses were conducted to evaluate the relationship between mortality, incidence, and DCI. In this study, we found that DCI was positively correlated with incidence (adjusted risk ratio [aRR] = 1.01, 95% [confidence interval, CI] = 1.00-1.02, p < 0.01). Higher correlation between mortality and DCI (mortality rate: r = 0.397, p = 0.018; mortality per 1,000,000 people: r = 0.0.428, p = 0.004) was observed than disease incidence. DCI remained statistically associated with mortality per 1,000,000 people after adjustment of Health Care Index (aRR = 1.02, 95% CI = 1.01-1.03, p < 0.001) or Healthcare Access and Quality Index (aRR = 1.02, 95% CI = 1.01-1.04, p < 0.01. Reducing DCI through strict infection control measures can help slow the increasing number of COVID-19 cases and further improve outcome in COVID-19 patients.

negative: The journey of remdesivir: from Ebola to COVID-19 Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

negative: One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome PURPOSE: Advances in supportive care and ventilator management for acute respiratory distress syndrome (ARDS) have resulted in declines in short-term mortality, but risks of death after survival to hospital discharge have not been well described. Our objective was to quantify the difference between short-term and long-term mortality in ARDS and to identify risk factors for death and causes of death at 1 year among hospital survivors. METHODS: This multi-intensive care unit, prospective cohort included patients with ARDS enrolled between January 2006 and February 2010. We determined the clinical characteristics associated with in-hospital and 1-year mortality among hospital survivors and utilized death certificate data to identify causes of death. RESULTS: Of 646 patients hospitalized with ARDS, mortality at 1 year was substantially higher (41 %, 95 % CI 37–45 %) than in-hospital mortality (24 %, 95 % CI 21–27 %), P < 0.0001. Among 493 patients who survived to hospital discharge, the 110 (22 %) who died in the subsequent year were older (P < 0.001) and more likely to have been discharged to a nursing home, other hospital, or hospice compared to patients alive at 1 year (P < 0.001). Important predictors of death among hospital survivors were comorbidities present at the time of ARDS, and not living at home prior to admission. ARDS-related measures of severity of illness did not emerge as independent predictors of mortality in hospital survivors. CONCLUSIONS: Despite improvements in short-term ARDS outcomes, 1-year mortality is high, mostly because of the large burden of comorbidities, which are prevalent in patients with ARDS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-013-3186-3) contains supplementary material, which is available to authorized users.

negative: Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.

negative: In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect Abstract Human coronaviruses SARS-CoV-2 appeared at the end of 2019 and led to a pandemic with high morbidity and mortality. As there are currently no effective drugs targeting this virus, drug repurposing represents a short-term strategy to treat millions of infected patients at low costs. Hydroxychloroquine showed an antiviral effect in vitro. In vivo it showed efficacy, especially when combined with azithromycin in a preliminary clinical trial. Here we demonstrate that the combination of hydroxychloroquine and azithromycin has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.

negative: Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling all Asymptomatic Patients Before Surgical Treatment BACKGROUND: In December 2019, a novel coronavirus was identified as the cause of many pneumonia cases in China and eventually declared as a pandemic as the virus spread globally. Few reports were published on the outcome of surgical procedures in diagnosed COVID-19 patients and even fewer on the surgical outcomes of asymptomatic undiagnosed COVID-19 surgical patients. We aimed to review all published data regarding surgical outcomes of preoperatively asymptomatic untested coronavirus disease 2019 (COVID-19) patients. METHODS: This report is a review on the perioperative period in COVID-19 patients who were preoperatively asymptomatic and not tested for COVID-19. Searches were conducted in PubMed April 4th, 2020. All publications, of any design, were considered for inclusion. RESULTS: Four reports were identified through our literature search, comprising 64 COVID-19 carriers, of them 51 were diagnosed only in the postoperative period. Synthesis of these reports, concerning the postoperative outcomes of patients diagnosed with COVID-19 during the perioperative period, suggested a 14/51 (27.5%) postoperative mortality rate and severe mostly pulmonic complications, as well as medical staff exposure and transmission. CONCLUSIONS: COVID-19 may have potential hazardous implications on the perioperative course. Our review presents results of unacceptable mortality rate and a high rate of severe complications. These observations warrant further well-designed studies, yet we believe it is time for a global consideration of sampling all asymptomatic patients before surgical treatment.

negative: Electrophysiology in the time of coronavirus: coping with the great wave. Aims: To chart the effect of the COVID-19 pandemic on the activity of interventional electrophysiology services in affected regions. Methods: We reviewed the electrophysiology laboratory records in 3 affected cities: Wenzhou in China, Milan in Italy and London, United Kingdom. We interviewed electrophysiologists in each centre to gather information on the impact of the pandemic on working patterns and on the health of staff members. Results: There was a striking decline in interventional electrophysiology activity in each of the centres. The decline occurred within a week of the recognition of widespread community transmission of the virus in each region and shows a striking correlation with the national figures for new diagnoses of COVID-19 in each case. During the period of restriction, work-flow dropped to <5% of normal, consisting of emergency cases only. In 2 of 3 centres, electrophysiologists were redeployed to perform emergency work outside electrophysiology. Among the centres studied, only Wenzhou has seen a recovery from the restrictions in activity. Following an intense nationwide program of public health interventions, local transmission of COVID-19 ceased to be detectable after February 18th allowing the electrophysiology service to resume with a strict testing regime for all patients. Conclusion: Interventional electrophysiology is vulnerable to closure in times of great social difficulty including the COVID-19 pandemic. Intense public health intervention can permit suppression of local disease transmission allowing resumption of some normal activity.

negative: Endocrinology in the time of COVID-19: Remodelling Diabetes Services and Promoting Innovation. The COVID-19 pandemic is a major international emergency leading to unprecedented medical, economic and societal challenges. Countries around the globe are facing challenges with diabetes care and are similarly adapting care delivery, with local cultural nuances. People with diabetes suffer disproportionately from acute COVID-19 with higher rates of serious complications and death. In-patient services need specialist support to appropriately manage glycaemia in people with known and undiagnosed diabetes presenting with COVID-19. Due to the restrictions imposed by the pandemic, people with diabetes may suffer longer-term harm caused by inadequate clinical support and less frequent monitoring of their condition and diabetes-related complications. Outpatient services need reorganised to maintain advice and support, focusing on proactive care for the highest risk, making use of telehealth and digital services for consultations, self-management and remote monitoring, where appropriate. Stratification of patients for face-to-face or remote follow-up should be based on a balanced risk assessment. Public health and national organisations have generally responded rapidly with guidance on care management, but the pandemic has created a tension around prioritisation of communicable vs non-communicable disease. Resulting challenges in clinical decision making are compounded by a reduced clinical workforce. For many years, increasing diabetes mellitus incidence has been mirrored by rising preventable morbidity and mortality due to complications, yet innovation in service delivery has been slow. While the current focus is on limiting the terrible harm caused by the pandemic, it is possible that a positive lasting legacy of COVID-19 might include accelerated innovation in chronic disease management.

negative: Neural Networks and Value at Risk Utilizing a generative regime switching framework, we perform Monte-Carlo simulations of asset returns for Value at Risk threshold estimation. Using equity markets and long term bonds as test assets in the global, US, Euro area and UK setting over an up to 1,250 weeks sample horizon ending in August 2018, we investigate neural networks along three design steps relating (i) to the initialization of the neural network, (ii) its incentive function according to which it has been trained and (iii) the amount of data we feed. First, we compare neural networks with random seeding with networks that are initialized via estimations from the best-established model (i.e. the Hidden Markov). We find latter to outperform in terms of the frequency of VaR breaches (i.e. the realized return falling short of the estimated VaR threshold). Second, we balance the incentive structure of the loss function of our networks by adding a second objective to the training instructions so that the neural networks optimize for accuracy while also aiming to stay in empirically realistic regime distributions (i.e. bull vs. bear market frequencies). In particular this design feature enables the balanced incentive recurrent neural network (RNN) to outperform the single incentive RNN as well as any other neural network or established approach by statistically and economically significant levels. Third, we half our training data set of 2,000 days. We find our networks when fed with substantially less data (i.e. 1,000 days) to perform significantly worse which highlights a crucial weakness of neural networks in their dependence on very large data sets ...

negative: Pangolin homology associated with 2019-nCoV To explore potential intermediate host of a novel coronavirus is vital to rapidly control continuous COVID-19 spread. We found genomic and evolutionary evidences of the occurrence of 2019-nCoV-like coronavirus (named as Pangolin-CoV) from dead Malayan Pangolins. Pangolin-CoV is 91.02% and 90.55% identical at the whole genome level to 2019-nCoV and BatCoV RaTG13, respectively. Pangolin-CoV is the lowest common ancestor of 2019-nCoV and RaTG13. The S1 protein of Pangolin-CoV is much more closely related to 2019-nCoV than RaTG13. Five key amino-acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and 2019-nCoV but four amino-acid mutations occur in RaTG13. It indicates Pangolin-CoV has similar pathogenic potential to 2019-nCoV, and would be helpful to trace the origin and probable intermediate host of 2019-nCoV.

negative: Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials Background: In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19. Method and analysis: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo. Ethics and dissemination: This study does not require ethical approval, because no participants data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal. Registration: This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript. Keywords: 2019 novel coronavirus, 2019-nCoV, Coronavirus diseases 2019, COVID-19, SARS-cov-2, Remdesivir, Randomized Controlled Trials. Systematic review, Meta-analysis, protocol

negative: Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.

negative: Sign‐on letter requests more flexibility in methadone treatment during COVID‐19 A sign‐on letter spearheaded by the National Alliance for Medication Assisted Recovery (NAMA), and harm reduction groups, including the Urban Survivors Union (USU) and the Drug Policy Alliance (DPA) is calling for reducing restrictions on methadone and opioid treatment programs (OTPs), so that patients don't have to go to the clinics so often. Included in the over 100 signatories are Patty McCarthy Metcalf of Faces & Voices of Recovery, Ben Levenson of the Levenson Foundation (and former founder of Origins) and many addiction physicians, as well as drug user organizations. Many of the signers have said for months that OTPs should be eliminated entirely.

negative: Coronavirus Disease 2019 in an Orthotopic Liver Transplant Recipient Living with Human Immunodeficiency Virus Coronavirus disease 2019 (COVID-19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with flu-like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID-19-infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID-19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well-controlled HIV who successfully recovered from a mild, flu-like illness attributed to SARS-CoV-2.

negative: An efficient microwave-assisted synthesis and biological properties of polysubstituted pyrimidinyl- and 1,3,5-triazinylphosphonic acids Abstract Polysubstituted pyrimidinylphosphonic and 1,3,5-triazinylphosphonic acids with potential biological properties were prepared in high yields by the microwave-assisted Michaelis–Arbuzov reaction of trialkyl phosphite with the corresponding halopyrimidines and halo-1,3,5-triazines, respectively, followed by the standard deprotection of the phosphonate group using TMSBr in acetonitrile. 4,6-Diamino-5-chloropyrimidin-2-ylphosphonic acid (7a) was found to exhibit a weak to moderate anti-influenza activity (28–50 μM) and may represent a novel hit for further SAR studies and antiviral improvement.

negative: Review of Chest CT Manifestations of COVID-19 Infection Coronavirus disease-19 (COVID-19) is a viral pandemic that started in China and has rapidly expanded worldwide. Typical clinical manifestations include fever, cough and dyspnea after an incubation period of 2-14 days. The diagnosis is based on RT-PCR test through a nasopharyngeal swab. Because of the pulmonary tropism of the virus, pneumonia is often encountered in symptomatic patients. Here, we review the pertinent clinical findings and the current published data describing chest CT findings in COVID-19 pneumonia, the diagnostic performance of CT for diagnosis, including differential diagnosis, as well the evolving role of imaging in this disease.

negative: Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study Background: The coronavirus disease 2019 (COVID-19) is spreading worldwide with 16,558 deaths till date. Serum albumin, high-density lipoprotein (HDL-C), and C-reactive protein have been known to be associated with the severity and mortality of community-acquired pneumonia. However, the characteristics and role of metabolic and inflammatory indicators in COVID-19 is unclear. Methods: We included 97 hospitalized patients with laboratory-confirmed COVID-19. Epidemiological, clinical, and laboratory indices; radiological features; and treatment were analysed. The differences in the clinical and laboratory parameters between mild and severe COVID-19 patients and the role of these indicators in severity prediction of COVID-19 were investigated. Results: All were Wuhan residents with contact with confirmed COVID-19 cases. The median age was 39 years (IQR: 30-59). The most common presenting symptoms were fever (58.8%), cough (55.7%), and fatigue (33%). Other features were lymphopenia, impaired fasting glucose, hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia. Decrease in lymphocyte count, serum total protein, serum albumin, high-density lipoprotein cholesterol (HDL-C), ApoA1, CD3+T%, and CD8+T% were found to be valuable in predicting the transition of COVID-19 from mild to severe illness. Chest computed tomography (CT) images showed that the absorption of bilateral lung lesions synchronized with the recovery of metabolic and inflammatory indicators. Conclusions: Hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia, and decreased ApoA1, CD3+T%, and CD8+T% could predict severity of COVID-19. Lymphocyte count, total serum protein, and HDL-C may be potentially useful for the evaluation of COVID-19.

negative: COVID-19 pandemic in the African continent: forecasts of cumulative cases, new infections, and mortality Background: Africa is the last major region to capitulate to the SARS-CoV-2 (COVID-19) pandemic. The first confirmed COVID-19 case in the region was reported on February 14, but what lies ahead in terms of the course and magnitude of infection remains speculative. To the best of our knowledge, no study, using a robust methodology, provides the immediate and long-term trajectory of COVID-19 for the entire region or accounts for its local context. This paper is the first systematic attempt to provide estimates on how many people would contract the virus and how many would die in the coming few months across Africa. Methods: The forecasts on caseloads and incidences are from a co-variate-based instrumental variable regression model. Fatality rates from Italy and China were further applied to generate mortality estimates after adjustments were made for differences in age-structure, health service quality, and living standards between each of the African countries and those of the reference population. We cover all countries that reported a confirmed case as of March 31, 2020. Results: By the end of June, 16,283,085 people will contract COVID-19 (95% CI 718,403 to 98, 358, 799). With a cumulative caseload of 5,413,4517 (95% CI 1,332,953 to 8,489,940) and 906,625 (95% CI 173, 821 to 4,742,917) Northern and Eastern Africa will respectively be the most and least affected sub-regions in the continent. Cumulative COVID-19 cases on June 30, 2020 are expected to reach 2,912, 864 (95% CI 465,028 to 18,286,358) in Southern Africa, 2,787, 913 (95% CI 517, 489 to 15,056,314) in Western Africa, and 1,185,742 (95% CI 229, 111 to 6,138,692) in Central Africa. New infections (incidence) for the month of April are expected to be the highest in Djibouti, 32.8 per 1000 (95% CI 6.25 to 171.77), while Morocco 1045 (95% CI 167 to 6,547) will register the highest number of deaths. Conclusion: Our study shows that countries that are least urbanized and have a low level of socio-economic development, hence least connected to the outside world, are likely to register lower and slower transmissions, at least at the early stage of the epidemic. However, the same set of enabling factors that worked for their benefit are likely to go against them in implementing interventions that have lessened the impact of the disease elsewhere.

negative: Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection Since the outbreak of the new coronavirus epidemic, novel coronavirus has infected nearly 100,000 people in more than 110 countries. How to face this new coronavirus epidemic outbreak is an important issue. Basic reproduction number (R0) is an important parameter in epidemiology; The basic reproduction number of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. Epidemiology dynamics is a mathematical model based on a susceptibility-infection-recovery epidemic model. Researchers analyzed the epidemiological benefits of different transmission rates for the establishment of effective strategy in prevention and control strategies for epidemic infectious diseases. In this review, the early use of TCM for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have wide application in treating infectious and non-infectious diseases. The TCM theoretical system of treating epidemic diseases with TCM and the treatment scheme of integrated Chinese and Western medicine have proved their effectiveness in clinical practice. TCM can cure COVID-19 pneumonia, and also shows that the role of TCM in blocking the progress of COVID-19 pneumonia.

negative: Treatments administered to the first 9,152 reported cases of COVID19: a systematic review Background The emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Repurposing existing drugs and rapidly launching clinical trials present the greatest near-term opportunities for mitigating COVID19s impact. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify and assess all treatments reported to be administered to COVID19 patients. Methods We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between Dec 1, 2019 and Mar 27, 2020. All studies reporting treatments were included. Data for each paper were manually extracted by two independent extractors. Outcomes included the duration from drug administration to clinically-meaningful response (complete symptom resolution or hospital discharge). Data were analysed descriptively. Results We identified 2,706 articles from single patient case reports to single-centre interventional studies. Of these, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalised, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a response time of 11.7 (1.09) days. Discussion A large number of treatments have been administered to the first 9,152 reported cases of COVID19. Further work is needed to prioritise drugs for investigation in well-controlled clinical trials and treatment protocols. Funding None.

negative: Coronavirus Disease 2019: A Comprehensive Review of Etiology, Pathogenesis, Diagnosis, and Ongoing Clinical Trials Coronavirus disease 2019 (COVID-19) is an acute respiratory viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease outbreak started in China in late December 2019 and quickly spread to the rest of the world, resulting in a pandemic. The incidence of cases is increasing every day, affecting millions of people around the globe and resulting in a public health emergency. Furthermore, disease management has been challenging for the clinicians and other medical personnel in terms of treatment options and availability of personal protective equipment. The off-label use of drugs such as hydroxychloroquine and emergency use authorization of remdesivir can hopefully help the clinicians while treating critically ill patients. The use of convalescent serum has also shown some interim benefit until a definitive treatment and preventive options are uncovered, such as vaccines and other effective treatment regimens.

negative: Recurrent Neural Network-based Acute Concussion Classifier using Raw Resting State EEG Data Concussion is a global health concern. Despite its high prevalence, a sound understanding of the mechanisms underlying this type of diffuse brain injury remains elusive. It is, however, well established that concussions cause significant functional deficits; that children and youths are disproportionately affected and have longer recovery time than adults; and recovering individuals are more prone to suffer additional concussions, with each successive injury increasing the risk of long term neurological and mental health complications. Currently, concussion management faces two significant challenges: there are no objective, clinically accepted, brain-based approaches for determining (i) whether an athlete has suffered a concussion, and (ii) when the athlete has recovered. Diagnosis is based on clinical testing and self-reporting of symptoms and their severity. Self-reporting is highly subjective and symptoms only indirectly reflect the underlying brain injury. Here, we introduce a deep learning Long Short Term Memory (LSTM)-based recurrent neural network that is able to distinguish between healthy and acute post-concussed adolescent athletes using only a short (i.e. 90 seconds long) sample of resting state EEG data as input. The athletes were neither required to perform a specific task nor subjected to a stimulus during data collection, and the acquired EEG data was neither filtered, cleaned of artefacts, nor subjected to explicit feature extraction. The LSTM network was trained and tested on data from 27 male, adolescent athletes with sports related concussion, bench marked against 35 healthy, adolescent athletes. During rigorous testing, the classifier consistently identified concussions with an accuracy of >90% and its ensemble-median Area Under the Curve (AUC) corresponds to 0.971. This is the first instance of a high-performing classifier that relies only on easy-to-acquire resting state EEG data. It represents a key step towards the development of an easy-to-use, brain-based, automatic classification of concussion at an individual level.

negative: Recurrent positive SARS‐CoV‐2: Immune certificate may not be valid Currently, coronavirus disease in 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1 has become a global pandemic. The presence of SARS-CoV-2 in COVID-19 patients is usually confirmed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) method.2 This article is protected by copyright. All rights reserved.

negative: Keeping the Country Positive during the COVID 19 Pandemic: Evidence from India

negative: A unified activities-based approach to the modelling of viral epidemics and COVID-19 as an illustrative example A new approach to formulating mathematical models of increasing complexity to describe the dynamics of viral epidemics is proposed. The approach utilizes a map of social interactions characterizing the population and its activities and, unifying the compartmental and the stochastic viewpoints, offers a framework for incorporating both the patterns of behaviour studied by sociological surveys and the clinical picture of a particular infection, both for the virus itself and the complications it causes. The approach is illustrated by taking a simple mathematical model developed in its framework and applying it to the ongoing pandemic of SARS-CoV-2 (COVID-19), with the UK as a representative country, to assess the impact of the measures of social distancing imposed to control its course.

negative: Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series OBJECTIVE: A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19. CASES: COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO2. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers. RESULTS: All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition. CONCLUSION: This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.

negative: Rhinovirus and Coronavirus Infection-Associated Hospitalizations among Older Adults Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults.

negative: 2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China The outbreak of COVID-19 originated in Wuhan has become a global epidemic of contagious diseases, which poses a serious threat to human life and health, especially for those with underlined diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients are still unknown. In this report, we reviewed the whole course of the epidemic emerged in the HD center of Renmin Hospital, Wuhan University from January 14, 2020, the day the first case was confirmed, to February 17, 2020, the day the epidemic extinction. There are totally 37 cases among 230 HD patients and 4 cases among 33 staff being diagnosed with COVID-19. The epidemiology, clinical presentation and immune profile of dialysis patients contracted COVID-19 were further studied. We found that the two key measures we took in response to the epidemic, one was upgrading level of prevention and protection on January 21 and the other one starting universal screening, isolating, and distributing the infected cases on February 4, were effective in the epidemic control. No new COVID-19 case had been diagnosed since February 13. During the epidemic, 7 HD patients died, including 6 with COVID-19 and 1 without COVID-19. The presumed causes of death were not directly related to pneumonia, but due to cardiovascular and cerebrovascular diseases, hyperkalemia, etc. Most of the leukocytes in the peripheral blood of the HD patients infected with COVID-19 decreased, and the CT images of the chest mostly showed the ground glass like changes on the right side. The symptoms of most of the patients were mild, and there were no cases admitted to ICU. The frequency of lymphocytes in PBMCs and the serum level of inflammatory cytokines were assessed in HD patients contracted COVID-19 or not, non-HD COVID-19 patients, as well as healthy volunteers. The results showed that lymphocytes of T cell, Th cells, killer T cells, as well as NK cells in PBMCs of HD patients decreased significantly than other groups. HD patients with COVID-19 also displayed remarkable lower serum level of inflammatory cytokines than other COVID-19 patients. Our study indicates that HD patients are the highly susceptible population and HD centers are high risk area in the outbreak of COVID-19 epidemic. Measures of prevention, protection, screening, isolation, and distribution are essential in the epidemic management and should be taken in the early stage. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

negative: Acute kidney injury at early stage as a negative prognostic indicator of patients with COVID-19: a hospital-based retrospective analysis Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient's prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08, P<0.001). In conclusion, male elderly COVID-19 patients with diabetes are more susceptible to AKI. AKI at early stage may be a negative prognostic indicator for COVID-19.

negative: COVID-19: towards controlling of a pandemic

negative: Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence Abstract The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no “specific drug” available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, “conventional drug in new use” becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the “specific drug”. China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.

negative: Convalescent plasma treatment of severe COVID-19: A matched control study Background Since December 2019, Coronavirus Disease 2019 (COVID-19) has become a global pandemic, causing mass morbidity and mortality. Prior studies in other respiratory infections suggest that convalescent plasma transfusion may offer benefit to some patients. Here, the outcomes of thirty-nine hospitalized patients with severe to life-threatening COVID-19 who received convalescent plasma transfusion were compared against a cohort of retrospectively matched controls. Methods Plasma recipients were selected based on supplemental oxygen needs at the time of enrollment and the time elapsed since the onset of symptoms. Recipients were transfused with convalescent plasma from donors with a SARS-CoV-2 (severe acute respiratory disease coronavirus 2) anti-spike antibody titer of [≥]1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls. Results Convalescent plasma recipients were more likely than control patients to remain the same or have improvements in their supplemental oxygen requirements by post-transfusion day 14, with an odds ratio of 0.86 (95% CI: 0.75~0.98; p=0.028). Plasma recipients also demonstrated improved survival, compared to control patients (log-rank test: p=0.039). In a covariates-adjusted Cox model, convalescent plasma transfusion improved survival for non-intubated patients (hazard ratio 0.19 (95% CI: 0.05 ~0.72); p=0.015), but not for intubated patients (1.24 (0.33~4.67); p=0.752). Conclusions Convalescent plasma transfusion is a potentially efficacious treatment option for patients hospitalized with COVID-19; however, these data suggest that non-intubated patients may benefit more than those requiring mechanical ventilation.

negative: Simultaneous Concentration of Bovine Viruses and Agricultural Zoonotic Bacteria from Water Using Sodocalcic Glass Wool Filters Infiltration and runoff from manured agricultural fields can result in livestock pathogens reaching groundwater and surface waters. Here, we measured the effectiveness of glass wool filters to simultaneously concentrate enteric viruses and bacteria of bovine origin from water. The recovery efficiencies were determined for bovine viral diarrhea virus types 1 and 2, bovine rotavirus group A, bovine coronavirus, poliovirus Sabin III, toxigenic Escherichia coli ,and Campylobacter jejuni seeded into water with three different turbidity levels (0.5, 215, and 447 NTU). Twenty liters of dechlorinated tap water (pH 7) were seeded with the test organisms, and then passed through a glass wool filter using a peristaltic pump (flow rate = 1 liter min(−1)). Retained organisms were eluted from the filters by passing beef extract-glycine buffer (pH 9.5) in the direction opposite of sample flow. Recovered organisms were enumerated by qPCR except for C. jejuni, which was quantified by culture. Mean recovery efficiencies ranged from 55 to 33 % for the bacteria and 58 to 16 % for the viruses. Using bootstrapping techniques combined with Analysis of Variance, recovery efficiencies were found to differ among the pathogen types tested at the two lowest turbidity levels; however, for a given pathogen type turbidity did not affect recovery except for C. jejuni. Glass wool filtration is a cost-effective method for concentrating several waterborne pathogens of bovine origin simultaneously, although recovery may be low for some specific taxa such as bovine viral diarrhea virus 1.

negative: Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19) A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

negative: Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.

negative: Tropical Medicine & International Health March 2020.

negative: Analysis of the clinical characteristics, drug treatments and prognoses of 136 patients with coronavirus disease 2019 WHAT IS KNOWN AND OBJECTIVE: Since the December 2019 discovery of several cases of coronavirus disease 2019 (COVID‐19) in Wuhan, China, the infection has spread worldwide. Our aim is to report on the clinical characteristics, treatments and prognoses of COVID‐19. METHODS: This was a retrospective, single‐centre, case series of 136 patients who were diagnosed with COVID‐19 at Wuhan Third Hospital in Wuhan, China, between 28 January 2020 and 12 February 2020. The clinical characteristics, laboratory tests, treatment features and prognoses were summarized. RESULTS AND DISCUSSION: The 136 patients were divided into a moderate (M) group (n = 103, 75.7%) and a severe and critical (SC) group (n = 33, 24.3%). There were significant differences in the incidences of concomitant chronic medical illnesses (eg, hypertension, diabetes and cardiovascular disease), fever, dry cough and dyspnoea among the two groups (P < .05). Compared with those in the M group, lymphocyte count (LYM) decreased significantly in the SC group, while the serum levels of C‐reactive protein (CRP), procalcitonin (PCT), creatinine (Cre), D‐dimer, lactic dehydrogenase (LDH), myoglobin (MB) and troponin I (cTnl) increased significantly in the SC group (P < .05). The main therapeutic drugs were antivirals, antibiotics, glucocorticoids, immunomodulators, traditional Chinese medicine preparations and symptomatic support drugs. There were significant differences in the incidences of shock, myocardial injury, acute respiratory distress syndrome (ARDS) and renal injury among the two groups (P < .05). Among the 136 patients, 99 (72.7%) were cured, 14 (10.3%) were transferred to other hospital and 23 (16.9%) died. WHAT IS NEW AND CONCLUSION: Elderly patients with chronic diseases are more likely to develop severe or critical COVID‐19 with multiple organ damage or systemic injuries. The improvement of LYM and CRP may be associated with the prognoses of COVID‐19. The combined use of three or more antiviral drugs is to be avoided. The combination of broad‐spectrum antibacterial drugs is not recommended and the risk of drug‐induced liver injury should be monitored. Throughout a patient's hospitalization, their treatment plan should be evaluated and adjusted according to their vital signs, clinical symptoms, laboratory tests and imaging changes. Patients should receive effective psychological counselling.

negative: CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity Abstract Purpose To report CT features of coronavirus disease-2019 (COVID-19) in patients with various disease severity. Methods The CT manifestations and clinical data of 73 patients with COVID-19 were retrospectively collected in 6 hospitals from Jan 21 to Feb 3, 2020. We analyzed the initial and follow-up CT features of patients with disease severity, according to the Guidelines for the Diagnosis and Treatment of New Coronavirus Pneumonia. Results Six patients (8%) were diagnosed as mild type pneumonia; these patients had no obvious abnormal CT findings or manifested mild changes of lung infection. All 43 patients (59 %) with common type presented unique or multiple ground-glass opacities (GGO) in the periphery of the lungs, with or without interlobular septal thickening. In the 21 patients (29 %) with severe type, extensive GGO and pulmonary consolidation were found in 16 cases (16/21, 76 %) and 5 cases (24 %), respectively. An extensive "white lung", with atelectasis and pleural effusion were found in critical type patients (3, 4%). On the resolutive phase of the disease, CT abnormalities showed complete resolution, or demonstrated residual linear opacities. Conclusions Different CT features are seen according to disease severity, which can help COVID-19 stratification.

negative: Supporting adults bereaved through COVID-19: a rapid review of the impact of previous pandemics on grief and bereavement The global COVID-19 pandemic is likely to have a major impact on the experience of death, dying and bereavement. This study aimed to review and synthesise learning from previous literature focused on the impact on grief and bereavement during other infectious disease outbreaks. We conducted a rapid scoping review according to the principles of the Joanna Briggs Institute and analysed qualitative data using thematic synthesis. From the 218 identified papers, 6 were included in the analysis. They were four qualitative studies, one observational study and a systematic review. Studies were conducted in West Africa, Haiti and Singapore. No research studies have focused on outcomes and support for bereaved people during a pandemic. Studies have tended to focus on survivors i.e. those who had the illness and recovered, recognising that some of these individuals will also be bereaved people. Previous pandemics appear to cause multiple losses both directly related to death itself but also in terms of disruption to social norms, rituals and mourning practices. This affects the ability for an individual to connect with the deceased both before and after the death, potentially increasing the risk of complicated grief. In view of the limited research, specific learning from the current COVID-19 crisis and the impact on the bereaved would be pertinent. Current focus should include innovative ways to promote connection and adapt rituals while maintaining respect. Strong leadership and coordination between different bereavement organisations is essential to providing successful post-bereavement support.

negative: The modelling of COVID19 pathways sheds light on mechanisms, opportunities and on controversial interpretations of medical treatments. v2 The new coronavirus (2019-nCoV or SARS-CoV2), inducing the current pandemic disease (COVID-19) and causing pneumoniae in humans, is dramatically increasing in epidemic scale since its first appearance in Wuhan, China, in December 2019. The first infection from epidemic coronaviruses in 2003 fostered the spread of an overwhelming amount of related scientific efforts. The manifold aspects that have been raised, as well as their redundancy offer precious information that has been underexploited and needs to be critically re-evaluated, appropriately used and offered to the whole community, from scientists, to medical doctors, stakeholders and common people. These efforts will favour a holistic view on the comprehension, prevention and development of strategies (pharmacological, clinical etc) as well as common intervention against the new coronavirus spreading. Here we describe a model that emerged from our analysis that was focused on the Renin Angiotensin System (RAS) and the possible routes linking it to the viral infection. because the infection is mediated by the viral receptor on human cell membranes Angiotensin Converting Enzyme (ACE2), which is a key component in RAS signalling. The model depicts the main pathways determining the disease and the molecular framework for its establishment, and can help to shed light on mechanisms involved in the infection. It promptly gives an answer to some of the controversial, and still open, issues concerning predisposing conditions and medical treatments that protect from or favour the severity of the disease (such as the use of ACE inhibitors or ARBs/sartans), or to the sex related biases in the affected population. The model highlights novel opportunities for further investigations, diagnosis and appropriate intervention to understand and fight COVID19.

negative: The effects of injection of bovine vaccine into a human digit: a case report BACKGROUND: The incidence of needlestick injuries in farmers and veterinary surgeons is significant and the consequences of such an injection can be serious. CASE PRESENTATION: We report accidental injection of bovine vaccine into the base of the little finger. This resulted in increased pressure in the flexor sheath causing signs and symptoms of ischemia. Amputation of the digit was required despite repeated surgical debridement and decompression. CONCLUSION: There have been previous reports of injection of oil-based vaccines into the human hand resulting in granulomatous inflammation or sterile abscess and causing morbidity and tissue loss. Self-injection with veterinary vaccines is an occupational hazard for farmers and veterinary surgeons. Injection of vaccine into a closed compartment such as the human finger can have serious sequelae including loss of the injected digit. These injuries are not to be underestimated. Early debridement and irrigation of the injected area with decompression is likely to give the best outcome. Frequent review is necessary after the first procedure because repeat operations may be required.

negative: Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively The reverse transcription polymerase chain reaction (RT-PCR) results for patients’oropharyngeal swab, stool, urine, and serum samples were collected and analyzed Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study In total, 28 (42 4%) women and 38 men (57 6%) with a median age of 44 0 (34 0–62 0) years were analyzed After in-hospital treatment, patients’inflammatory indicators decreased with improved clinical condition The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9 5 (6 0–11 0) days By February 10, 2020, 11 convalescent patients (16 7%) still tested positive for viral RNA from stool specimens and the other 55 patients’stool specimens were negative for 2019-nCoV following a median duration of 11 0 (9 0–16 0) days after symptom onset Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2 0 (1 0–4 0) days Results for only four (6 9%) urine samples were positive for viral nucleic acid out of 58 cases;viral RNA was still present in three patients’urine specimens after throat swabs were negative Using a multiple linear regression model ( F =2 669, P =0 044, and adjusted R 2 =0 122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’stools ( t =-2 699, P =0 010) The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8 0 days, respectively;t =2 550, P =0 013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively;t =4 631, P <0 001) There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results ( P >0 05) Conclusions: In brief, as the clearance of viral RNA in patients’stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease The duration of RNA detection may relate to host cell immunity

negative: Systematic rapid "living" review on rehabilitation needs due to covid-19: update to march 31st 2020. BACKGROUND The outbreak of Covid-19 epidemics has challenged the provision of health care worldwide, highlighting the main flaws of some national health systems with respect to their capacity to cope with the needs of frail subjects. People experiencing disability due to Covid-19 express specific rehabilitation needs that deserve a systematic evidence-based approach. OBJECTIVES To provide the rehabilitation community with updates on the latest scientific literature on rehabilitation needs due to Covid-19. The first rapid "living" review will present the results of a systematic search performed up to March 31st, 2020. METHODS A systematic search on PubMed, Pedro and Google Scholar was performed using the search terms: "Covid-19", "Coronavirus", "severe acute respiratory syndrome coronavirus 2", "rehabilitation", "physical therapy modalities", "exercise", "occupational therapy", and "late complications". Papers published up to March 31st, 2020, in English, were included. RESULTS Out of the 2758 articles retrieved, 9 were included in the present review. Four of them are "calls for action", 3 provide recommendations about rehabilitation interventions in the acute phase, 2 address the needs of people quarantined at home or with restricted mobility due to the lockdown, and 1 provides a Core Outcome Set to be used in clinical trials to test the efficacy of health strategies in managing Covid-19 patients. CONCLUSIONS All selected papers were based on previous literature and not on the current Covid-19 pandemic. Main messages included: 1) early rehabilitation should be granted to inpatients with Covid-19; 2) people with restricted mobility due to quarantine or lockdown should receive exercise programs to reduce the risk of frailty, sarcopenia, cognitive decline and depression; 3) telerehabilitation may represent the first option for people at home. Further updates are warranted in order to characterize the emerging disability in Covid-19 survivors and the adverse effects on the health of chronically disabled people.

negative: Short-term outcomes in individuals aged 75 or older with severe coronavirus disease (COVID-19): First observations from an Infectious Diseases Unit in Southern Italy

negative: Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review. Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.

negative: Statistics based predictions of coronavirus 2019-nCoV spreading in mainland China Background. The epidemic outbreak cased by coronavirus 2019-nCoV is of great interest to researches because of the high rate of spread of the infection and the significant number of fatalities. A detailed scientific analysis of the phenomenon is yet to come, but the public is already interested in the questions of the duration of the epidemic, the expected number of patients and deaths. For long time predictions, the complicated mathematical models are necessary which need many efforts for unknown parameters identification and calculations. In this article, some preliminary estimates will be presented. Objective. Since the reliable long time data are available only for mainland China, we will try to predict the epidemic characteristics only in this area. We will estimate some of the epidemic characteristics and present the most reliable dependences for victim numbers, infected and removed persons versus time. Methods. In this study we use the known SIR model for the dynamics of an epidemic, the known exact solution of the linear equations and statistical approach developed before for investigation of the children disease, which occurred in Chernivtsi (Ukraine) in 1988-1989. Results. The optimal values of the SIR model parameters were identified with the use of statistical approach. The numbers of infected, susceptible and removed persons versus time were predicted. Conclusions. Simple mathematical model was used to predict the characteristics of the epidemic caused by coronavirus 2019-nCoV in mainland China. The further research should focus on updating the predictions with the use of fresh data and using more complicated mathematical models.

negative: The connection of growth and medication of COVID-19 affected people after 30 days of lock down in India The COVID-19 pandemic has already consumed few months of indolence all over the world. Almost every part of the world from which the victim of COVID 19 are, have not yet been able to find out a strong way to combat corona virus. Therefore, the main aim is to minimize the spreading of the COVID-19 by detecting most of the affected people during lockdown. Hence, it is necessary to understand what the nature of growth is of spreading of this corona virus with time after almost one month (30 days) of lockdown. In this paper we have developed a very simple mathematical model to describe the growth of spreading of corona virus in human being. This model is based on realistic fact and the statistics we have so far. For controlling the spread of the COVID-19, minimization of the growth with minimum number of days of lockdown is necessary. We have established a relation between the long-term recovery coefficient and the long-term infected coefficient. The growth can be minimized if such condition satisfies. We have also discussed how the different age of the people can be cured by applying different types of medicine. We have presented the data of new cases, recovery and deaths per day to visualize the different coefficient for India and establish our theory. We have also explained how the medicine could be effective to sustain and improve such condition for country having large population like India.

negative: Society of General Internal Medicine: 28th Annual Meeting New Orleans, LA May 11–14, 2005: Out of Chaos: The Critical Role of Generalists, ABSTRACTS OF SUBMISSIONS ACCEPTED FOR PRESENTATIOIN

negative: Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

negative: A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.

negative: Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

negative: More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people’s attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. METHODS: Using Google Trends, we retrieved public query data for terms of “2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019” between the 31(st) December 2019 and the 24(th) February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. RESULTS: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31(st) January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. CONCLUSIONS: The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally.

negative: COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2-14 days, and mostly 3-7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.

negative: Anaesthetic managment and clinical outcomes of parturients with COVID-19: a multicentre, retrospective, propensity score matched cohort study Objective:To analyse the clinical features of COVID-19 parturients, and to compare anaesthetic regimen and clinical outcomes in parturients with or without COVID-19 undergoing cesarean delivery.Methods: Data were extracted from the electronic medical record of 3 medical institutions in Hubei Province, China, from June 1, 2019 to March 20, 2020 according to inclusion and exclusion criteria. After propensity score matching with demographics, the clinical and laboratory characteristics of parturients with or without COVID-19 were analysed. The anaesthetic regimen and clinical outcomes of themselves and their infants were compared in these two groups of parturients. Results: A total of 1,588 patients without SARS-CoV-2 infection undergoing cesarean delivery were retrospectively included. After achieving a balanced cohort through propensity score matching, 89 patients (COVID-19 group), who were diagnosed with COVID-19 by SARS-CoV-2 nucleic acid test and CT scan matched with 173 patients without COVID-19 (Control group). The SARS-CoV-2 infected parturients in the early stages of COVID-19 outbreak was much more than during the later stage. The main clinical characteristics of parturients with COVID-19 were fever (34.8%), cough (33.7%), an increased plasma CRP (52.8%) and a decreased lymphocyte counting (33.7%). A high rate of emergency and a high incidence of anaesthesia-related complications, such as pharyngalgia, multiple puncture, intraoperative hypotension, nausea, vomiting, vertigo and chills in the COVID-19 parturients. In addition, the parturients with COVID-19 had a long duration of operation and hospital stay, and an increased intraoperative oxytocin utilization and postoperative oxygen therapy. The newborns from the SARS-CoV-2 infected mothers, who received general anaesthesia, had a high risk of Apgar score [≤]8 at 1 and 5 minutes after delivery and a higher rate of neonatal intensive care unit (NICU) admission. Conclusions: Anaesthesia-related complications occur more frequently in the COVID-19 parturients and their newborns have a high risk of distress.

negative: Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) IMPORTANCE: Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. OBJECTIVE: To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. MAIN OUTCOMES AND MEASURES: Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. RESULT: Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro–brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168). CONCLUSIONS AND RELEVANCE: Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.

negative: Data Driven Modeling of Projected Mitigation and Suppressing Strategy Interventions for SARS-COV 2 in Ghana In the midst of pandemic for respiratory illness, the call for non-pharmaceutical interventions become the highest priority for infectious disease and public health experts, while the race towards vaccine or medical intervention are ongoing. Individuals may modify their behavior and take preventative steps to reduce infection risk in the bid to adhere to the call by government officials and experts. As a result, the existence of relationship between the preliminary and the final transmission rates become feeble. This study evaluates the behavioral changes (mitigation and suppression measures) proposed by public health experts for COVID-19 which had altered human behavior and their day to day lives. The dynamics underlying the mitigation and suppression measures reduces the contacts among citizens and significantly interfere with their physical and social behavior. The results show all the measures have a significant impact on the decline of transmission rate. However, the mitigation measures might prolong the elimination of the transmission which might lead to a severe economic meltdown, yet, a combination of the measures show a possibility of rooting out transmission within 30 days if adhered to in an extreme manner. The result shows a peak period of infection for Ghana ranges from 64th day to 74th day of infection time period.

negative: Evidence from internet search data shows information-seeking responses to news of local COVID-19 cases The COVID-19 outbreak is a global pandemic with community circulation in many countries, including the United States, with confirmed cases in all states. The course of this pandemic will be shaped by how governments enact timely policies and disseminate information and by how the public reacts to policies and information. Here, we examine information-seeking responses to the first COVID-19 case public announcement in a state. Using an event study framework for all US states, we show that such news increases collective attention to the crisis right away. However, the elevated level of attention is short-lived, even though the initial announcements are followed by increasingly strong policy measures. Specifically, searches for "coronavirus" increased by about 36% (95% CI: 27 to 44%) on the day immediately after the first case announcement but decreased back to the baseline level in less than a week or two. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms, and hand sanitizer. On the other hand, searches for information regarding community-level policies (e.g., quarantine, school closures, testing) or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are representative of the study period being relatively early in the epidemic, and more-elaborate policy responses were not yet part of the public discourse. Further analysis should track evolving patterns of responses to subsequent flows of public information.

negative: Single incision laparoscopic cholecystectomy (SILC) versus laparoscopic cholecystectomy (LC)-a matched pair analysis. INTRODUCTION The aim of our study was to compare single incision laparoscopic cholecystectomy (SILC) and laparoscopic cholecystectomy (LC) with respect to complications, operating time, postoperative pain, use of analgesics, length of stay, return to work, rate of incisional hernia, and cosmetic outcome. METHODS Sixty-seven patients underwent SILC. Of a cohort of 163 LC operated in the same time period, 67 patients were chosen for a matched pair analysis. Pairs were matched for age, gender, ASA, BMI, acuity, and previous abdominal surgery. In the SILC group, patient characteristics (gender, age, BMI, comorbidities, ASA, previous abdominal surgery, symptomatic cholecystolithiasis, cholecystitis) and perioperative data (surgeon, operation time, conversion rate and cause, intraoperative complications, postoperative complications, reoperation rate, VAS at 24 h, VAS at 48 h, use of analgesics according to WHO class, and length of stay) were collected prospectively. RESULTS Follow-up in the SILC and LC group was completed with a minimum of 17 and a maximum of 26 months; data acquired were recovery time the patients needed until they were able to get back into the working process, long-term incidence of postoperative hernias, and satisfaction with cosmetic outcome. Operating time was longer for SILC (median 75 min, range 39-168 vs. 63, range 23-164, p = 0.039). There were no significant differences for SILC and LC with regard to postoperative pain measured by VAS at 24 h (median 3, range 0-8 vs. 2, range 0-8, p = 0.224), at 48 h (median 2, range 0-6 vs. 2, range 0-8, p = 0.571), use of analgesics, and length of stay (median 2 days, range 1-9 vs. 2, range 1-11, p = 0.098). There was no major complication in either group. The completion rate of SILC was 85.1% (57 of 67). Although there was a trend towards an earlier return to the working process in patients of the SILC group, this was not significant. The rate of incisional hernias was 1.9% (1/53) in the SILC and 2.1% (1/48) in the LC group indicating no significant difference. Self-assessment of satisfaction with the cosmetic outcome was not judged different by patients in both groups. CONCLUSION SILC is associated with longer operating time, but equals LC with respect to safety, postoperative pain, use of analgesics, length of stay, return to work, rate of incisional hernia, and cosmetic outcome.

negative: Modeling and forecasting the early evolution of the Covid-19 pandemic in Brazil We model and forecast the early evolution of the COVID-19 pandemic in Brazil using Brazilian recent data from February 25, 2020 to March 30, 2020. This early period accounts for unawareness of the epidemiological characteristics of the disease in a new territory, sub-notification of the real numbers of infected people and the timely introduction of social distancing policies to flatten the spread of the disease. We use two variations of the SIR model and we include a parameter that comprises the effects of social distancing measures. Short and long term forecasts show that the social distancing policy imposed by the government is able to flatten the pattern of infection of the COVID-19. However, our results also show that if this policy does not last enough time, it is only able to shift the peak of infection into the future keeping the value of the peak in almost the same value. Furthermore, our long term simulations forecast the optimal date to end the policy. Finally, we show that the proportion of asymptomatic individuals affects the amplitude of the peak of symptomatic infected, suggesting that it is important to test the population.

negative: Preventive Behaviors Conveyed on YouTube to Mitigate Transmission of COVID-19: Cross-Sectional Study BACKGROUND: Accurate information and guidance about personal behaviors that can reduce exposure to severe acute respiratory syndrome coronavirus 2 are among the most important elements in mitigating the spread of coronavirus disease 2019 (COVID-19). With over 2 billion users, YouTube is a media channel that millions turn to when seeking information. OBJECTIVE: At the time of this study, there were no published studies investigating the content of YouTube videos related to COVID-19. This study aims to address this gap in the current knowledge. METHODS: The 100 most widely viewed YouTube videos uploaded throughout the month of January 2020 were reviewed and the content covered was described. Collectively, these videos were viewed over 125 million times. RESULTS: Fewer than one-third of the videos covered any of the seven key prevention behaviors listed on the US Centers for Disease Control and Prevention website. CONCLUSIONS: These results represent an important missed opportunity for disease prevention.

negative: Can Testing Ease Social Distancing Measures? Future Evolution of COVID-19 in NYC The"New York State on Pause"executive order came into effect on March 22 with the goal of ensuring adequate social distancing to alleviate the spread of COVID-19. Pause will remain effective in New York City in some form until early June. We use a compartmentalized model to study the effects of testing capacity and social distancing measures on the evolution of the pandemic in the"post-Pause"period in the City. We find that testing capacity must increase dramatically if it is to counterbalance even relatively small relaxations in social distancing measures in the immediate post-Pause period. In particular, if the City performs 20,000 tests per day and relaxes the social distancing measures to the pre-Pause norms, then the total number of deaths by the end of September can reach 250,000. By keeping the social distancing measures to somewhere halfway between the pre- and in-Pause norms and performing 100,000 tests per day, the total number of deaths by the end of September can be kept at around 27,000. Going back to the pre-Pause social distancing norms quickly must be accompanied by an exorbitant testing capacity, if one is to suppress excessive deaths. If the City is to go back to the"pre-Pause"social distancing norms in the immediate post-Pause period and keep the total number of deaths by the end of September at around 35,000, then it should be performing 500,000 tests per day. Our findings have important implications on the magnitude of the testing capacity the City needs as it relaxes the social distancing measures to reopen its economy.

negative: Impact of COVID-19 on Prostate Cancer Management: Guidelines for Urologists Abstract Context The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a global health emergency, the like of which has never been seen before. Prostate cancer (PCa) services across the globe have been on hold due to changing medical and surgical priorities. There is also epidemiological evidence that PCa patients have increased incidence and mortality from SARS-CoV-2 infection due to gender differences, age, and higher propensity for risk factors (eg, respiratory disease, obesity, hypertension, and smoking status). Objective To contribute to the emerging body of knowledge on the risks of SARS-CoV-2 infection to PCa patients and, in the face of PCa treatment delays, provide evidence-based recommendations for ongoing management of specific PCa patient groups. Evidence acquisition A literature search was performed using all sources (MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science) as well as the media to harness emerging data on the SARS-CoV-2 pandemic and its influence on PCa. Eligibility criteria were originality of data and relevance to PCa management. The authors note that during these unprecedented times, retrospective data are constantly being updated from multiple sources globally. Evidence synthesis A total of 72 articles and data sources were found initially. Owing to repetition, lack of originality, or nonrelevance, six articles were rejected, leaving 23 retrospective studies, seven basic science research articles, 15 societal and journal guidelines, and 21 epidemiological data sources, from countries at different stages of SARS-CoV-2 pandemic. These were analyzed qualitatively to produce evidence-based guidelines for the management of PCa patients at different stages of the patient journey, with strategies to reduce the risk of viral spread. Conclusions PCa patients may have an increased risk of SARS-CoV-2 infection as well as morbidity and mortality if infected. Once appropriately triaged, and to reduce viral spread, PCa patients can have surveillance by telemedicine, and institute lifestyle changes and social quarantining measures. If risk stratification suggests that treatment should be planned, androgen deprivation therapy can be started, or potentially surgery or radiation therapy is possible on a case-by-case basis. Patient summary Prostate cancer patients can be followed up remotely until the severe acute respiratory syndrome coronavirus 2 pandemic resolves, but higher-risk cases may have treatment expedited to limit any negative impact on prostate cancer outcomes.

negative: COVID-19 clinical characteristics, and sex-specific risk of mortality: Systematic Review and Meta-analysis Objectives: The rapidly evolving coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization on March 11, 2020. It was first detected in the city of Wuhan in China and has spread globally resulting in substantial health and economic crisis in many countries. Observational studies have partially identified the different aspects of this disease. Up to this date, no comprehensive systematic review for the clinical, laboratory, epidemiologic and mortality findings has been published. We conducted this systematic review and meta-analysis for a better understanding of COVID-19. Methods: We reviewed the scientific literature published from January 1, 2019 to March 3, 2020. Statistical analyses were performed with STATA (version 14, IC; Stata Corporation, College Station, TX, USA). The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. Publication bias was assessed and p <0.05 was considered a statistically significant publication bias. Results: Out of 1102 studies, 32 satisfied the inclusion criteria. A total of 4789 patients with a mean age of 49 years were evaluated. Fever (83.0%, CI 77.5 to 87.6), cough (65.2%, CI 58.6 to 71.2) and myalgia/fatigue (34.7, CI 26.0 to 44.4) were the most common symptoms. The most prevalent comorbidities were hypertension (18.5 %, CI 12.7 to 24.4) and Cardiovascular disease (14.9 %, CI 6.0 to 23.8). Among the laboratory abnormalities, elevated C-Reactive Protein (CRP) (72.0% (CI 54.3 to 84.6) and lymphopenia (50.1%, CI 38.0 to 62.4) were the most common findings. Bilateral ground-glass opacities (66.0%, CI 51.1 to 78.0) was the most common CT-Scan presentation. Pooled mortality rate was 6.6%, with males having significantly higher mortality compared to females (OR 3.4; 95% CI 1.2 to 9.1, P = 0.01). Conclusion: COVID-19 commonly presented with a progressive course of cough and fever with more than half of hospitalized patients showing leukopenia or a high CRP on their laboratory findings. Mortality associated with COVID19 was higher than that reported in studies in China with Males having a 3-fold higher risk of mortality in COVID19 compared to females.

negative: Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report Introduction: Novel coronavirus or coronavirus disease (COVID-19) can affect all age groups. The clinical course of the disease in children and infants is milder than in adults. It should be noted that, although typical symptoms may be present in children, non-specific symptoms could be noted in the neonate. The disease is rare in the neonate, so, its suspicion in this group can help to make a quick diagnose. Case report: A 15-day-old neonate was admitted with fever, lethargy, cutaneous mottling, and respiratory distress without cough. His mother had symptoms of Novel coronavirus. So Reverse-Transcription Polymerase Chain Reaction (RT-PCR) assay was done for the neonate and showed to be positive. The newborn was isolated and subjected to supportive care. Antibiotic and antiviral treatment was initiated. Eventually, the baby was discharged in good general condition. Conclusion: When a newborn presents with non-specific symptoms of infection with an added history of COVID-19 in his/her parents, it indicates the need for PCR testing for Novel coronavirus.

negative: Gastrointestinal cancer surgery and enhanced recovery after surgery (ERAS) during COVID-19 outbreak

negative: Follow-up Study on Pulmonary Function and Lung Radiographic Changes in Rehabilitating Severe Acute Respiratory Syndrome Patients After Discharge Objectives To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients. Methods Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status. Results Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (Dlco < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and Dlco ≥ 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. Dlco improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later. Conclusion These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. Dlco scores might be more sensitive than HRCT when evaluating lung fibrotic changes.

negative: Neurologic complications of COVID-19 BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barré syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.

negative: COVID-19, hypertension and cardiovascular diseases: Should we change the therapy? The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.

negative: The COVID-19 Pandemic: Setting the Mental Health Research Agenda

negative: Global, Regional and National Incidence and Case-fatality rates of Novel Coronavirus (COVID-19) across 154 countries and territories: A systematic assessment of cases reported from January to March 16, 2020 Background: The 2019 novel coronavirus disease (COVID-19) outbreak turned into a pandemic, with hundreds of thousands of cases reported globally. The number of cases dramatically increased beginning in early March 2020. Aim: We assessed the cumulative change in the incidence and case-fatality rates of COVID-19 at the global, regional, and national levels from January to March 16, 2020, in 154 affected countries and territories globally. Methods: We collected data of COVID-19 cases using the GitHub repository, which provided real-time surveillance information developed by the Center for Systems Science and Engineering (CSSE), Johns Hopkins University (USA). Information such as confirmed COVID-19 cases, deaths, and recoveries reported across all affected countries was collected from January 22 to March 16, 2020. We estimated the change in the incidence rate, case-fatality rate, and recovery rate from January 22 to February 29 and from March 1 to March 16, 2020. Results: From January 22 to March 16, 2020, globally, the number of incident COVID-19 cases increased by 276.2%, and Europe recorded 65,281 new cases from March 1 to 16, 2020. Overall, the case-fatality rate was 3.92%, with a high COVID-19 fatality rate in Italy (7.7%), Iran (5.7%), China (4.2%) and the United Kingdom (3.6%). The estimated percentage change in COVID-19 cases from March 1 to 16, 2020, was highest in Belgium (105.8/100,000 population), followed by Qatar (439/100,000 population) and Portugal (331/100,000 population). The overall recovery rate of COVID-19 was 43%; China (35.5%) had the highest recovery rate, while the United States of America recorded a recovery rate of 0.3%. Conclusion: Overall, all the COVID-19-affected countries showed an upward trend in incidence, with little change in the incidence rate of -0.20% from January to Mid-March. The case-fatality rate was found to be 3.92%, and the recovery rate was observed to be less than half (43%) among COVID-19 patients. Italy, Iran, and Spain had the largest numbers of new cases of COVID-19 from March 1 to 16, 2020.

negative: The psychological impact of COVID-19 on the mental health in the general population As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.

negative: The challenges and opportunities of a global health crisis: the management and business implications of COVID-19 from an Asian perspective On March 11, 2020, the World Health Organization (WHO) declared the coronavirus (COVID-19) outbreak a pandemic. As the evolution and implications of the COVID-19 crisis are still unfolding, we posit that exploring the experiences and strategic responses of Asian countries may shed light on ways to combat COVID-19 for the rest of the world. In this paper, we first articulate the importance of resilience, strategic agility, and entrepreneurship in the context of the fight against COVID-19. Then, with the focus on China, South Korea, and Singapore, we discuss the impact COVID-19 is having on economies and businesses, governmental support for businesses and societies, and implications for global supply chain disruptions. We hope that the global health system will recover quickly, and that the world economy will be revitalized with the contributions and collaboration of science (including social science), industry, and governments.

negative: COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review Coronavirus disease 2019 (COVID-19) was reported at the end of 2019 in China for the first time and has rapidly spread throughout the world as a pandemic. Since COVID-19 causes mild to severe acute respiratory syndrome, most studies in this field have only focused on different aspects of pathogenesis in the respiratory system. However, evidence suggests that COVID-19 may affect the central nervous system (CNS). Given the outbreak of COVID-19, it seems necessary to perform investigations on the possible neurological complications in patients who suffered from COVID-19. Here, we reviewed the evidence of the neuroinvasive potential of coronaviruses and discussed the possible pathogenic processes in CNS infection by COVID-19 to provide a precise insight for future studies.

negative: The comparison of trends in Spain and the Nederland: a Dynamical compartment model of the transmission of Coronavirus The recent spreading of coronavirus made many countries impose restrictions in order to control its dangerous effect on the citizens. We developed a theoretical dynamical model based on compartmental SIR system with additional adjustment taken from Flow network and Markov chain frameworks to illustrate developments and trends based on publicly available data. Based on this Model, code in R was written and fed by stamped publicly available data from authorized governmental websites in Spain and in the Nederlands, to compare trends. Our results show that the 'peak' of infection is already behind us in both countries, but also demonstrate that there is a danger of rebound of a spread. It is obvious that measures imposed are giving the results, but we should be precarious of near future practices and developments since the majority of population will still be without immunity.

negative: A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.

negative: SARS-CoV-2 outbreak: How can pharmacists help? Coronaviruses (CoVs) are a large family of viruses that cause disorders ranging from a mild cold to severe disease. Some of the CoVs are zoonotic, meaning they can be transmitted from animals to humans. In December 2019, the world awoke to a new zoonotic strain of CoV that was named SARS-CoV-2 (standing for severe acute respiratory syndrome coronavirus 2), which has been classified as a high-consequence infectious disease. In addition, serious complications related to COVID-19 have been reported in some patients. These include acute respiratory distress syndrome, acute renal failure, septic shock and ventilator-associated pneumonia. The pharmacist, as a healthcare practitioner, can play an important role in hindering the spread of COVID-19, and can be an active participant in national and community efforts to fight and contain this outbreak.

negative: Glycyrrhetinic acid and its derivatives as potential alternative medicine to relieve symptoms in nonhospitalized COVID‐19 patients SARS‐CoV‐2 is highly infectious, and infection by this virus results in COVID‐19, manifesting predominantly symptoms in the lower respiratory system. Detection of viral genomic materials by RT‐PCR is the gold standard for diagnosis. Suspected COVID‐19 patients who had a documented history of exposure and exhibited symptoms, but did not have positive PCR test results, were generally self‐quarantined with prescriptions aiming to help attenuate their symptoms. These prescriptions are however neither specific nor highly effective for COVID‐19 treatment. Given the rapidly growing pandemic and the overwhelmed medical system, the number of self‐quarantined patients is increasing. There is an urgent need of alternative medicine to help patients relieve symptoms during self‐quarantine, and to potentially help increase their chances of survival and recovery from the infection. We report here a case of severe COVID‐19 that never had a positive PCR test result during disease progression but was confirmed with antibody test post recovery. This patient was self‐quarantined and received diammonium glycyrrhizinate (DG), a steroid‐like molecule, in combination with vitamin C as alternative medicine. This patient went through severe COVID‐19 but eventually recovered upon the implementation of this treatment regimen, suggesting potential therapeutic effects of DG as alternative medicine to help relieve COVID‐19 symptoms.

negative: The outbreak of COVID-19: An overview In late December 2019, a previous unidentified coronavirus, currently named as the 2019 novel coronavirus#, emerged from Wuhan, China, and resulted in a formidable outbreak in many cities in China and expanded globally, including Thailand, Republic of Korea, Japan, United States, Philippines, Viet Nam, and our country (as of 2/6/2020 at least 25 countries). The disease is officially named as Coronavirus Disease-2019 (COVID-19, by WHO on February 11, 2020). It is also named as Severe Pneumonia with Novel Pathogens on January 15, 2019 by the Taiwan CDC, the Ministry of Health and is a notifiable communicable disease of the fifth category. COVID-19 is a potential zoonotic disease with low to moderate (estimated 2%–5%) mortality rate. Person-to-person transmission may occur through droplet or contact transmission and if there is a lack of stringent infection control or if no proper personal protective equipment available, it may jeopardize the first-line healthcare workers. Currently, there is no definite treatment for COVID-19 although some drugs are under investigation. To promptly identify patients and prevent further spreading, physicians should be aware of the travel or contact history of the patient with compatible symptoms.

negative: Anosmia and Ageusia: Common Findings in COVID‐19 Patients In a not negligible number of patients affected by COVID‐19 (coronavirus disease 2019), especially if paucisymptomatic, anosmia and ageusia can represent the first or only symptomatology present. Laryngoscope, 2020

negative: Estimation of protection for COVID-19 in children from epidemiological information and estimate effect of policy in Japan Background: Incidence in children was much less than in adults during the COVID−19 outbreak. Sports and entertainment events were canceled (VEC) in Japan for two weeks during 26 February − 13 March. Most schools were closed (SC). Object: We construct a susceptible−infected −recovered model using three age classes and estimate the basic reproduction number (R0) and protection level among children simultaneously. Then we simulate SC and VEC effects. Method: We used data of patients with symptoms in Japan during 14 January to assess SC and VEC introduction. Effects of SC and VEC were incorporated into the model through change in the contact pattern or frequencies among age classes. Results: Results suggest R0 as 2.86 [95%CI of 2.73, 2.97]. The protection level was estimated as 0.4 [0.2, 0.7]. SC and VEC can reduce the total number of patients significantly, by 6−7%. Discussion and Conclusion: The estimated R0 was similar to that found from other studies in China and Japan. We found a significant protection level among children, and by effects of SC and VEC. Introduction

negative: Early events of SARS coronavirus infection in vero cells An isolate from a patient in the recent severe acute respiratory syndrome (SARS) outbreak in Singapore was used to infect Vero E6 cells. This study concentrated on the first 30 min of infection. It was discovered that the SARS coronavirus attached, entered, and uncoated the nucleocapsids, all within a 30‐min period. At 5 min after infection, several virus particles lined the Vero cell plasma membrane. Virus particles were at various stages of fusion at the cell surface, since entry was not a synchronised process. After entry (10 and 15 min), spherical core particles moved into the cytoplasm within large vacuoles. Quite surprising at such early stages of infection (20 min), a virus‐induced change in the infected cells was evident. The induction of myelin‐like membrane whorls was obvious within the same vacuoles as the core particles. The significance of this virus‐induced change is unknown at this stage. By 25–30 min postinfection (p.i.), the spherical core particles appeared to be disassociating and, in their place, doughnut‐shaped electron‐dense structures were observed. These could be the virus genomes together with the helical nucleocapsids. They were no longer in large vacuoles but packaged into smaller vacuoles in the cytoplasm, and occasionally in small groups. J. Med. Virol. 71:323–331, 2003. © 2003 Wiley‐Liss, Inc.

negative: A Recovered Case of COVID-19 Myocarditis and ARDS Treated with Corticosteroids, Tocilizumab, and Experimental AT-001 Abstract: We describe the case of a critically-ill patient with myocarditis and severe ARDS related to COVID-19 infection. This case highlights management strategies including the use of corticosteroids, an IL-6 inhibitor, and an aldose reductase inhibitor resulting in complete clinical recovery.

negative: COVID-19: Peer Support and Crisis Communication Strategies to Promote Institutional Resilience Caring for patients with the novel coronavirus infection is placing great stress on health care systems and health care workers. On the basis of their experiences responding to other pandemics, the authors summarize lessons learned and offer some best practices for facilitating organizational resilience and supporting health care workers during the COVID-19 pandemic.

negative: Long-term outcome in acute myelogenous leukemia autografted with mafosfamide-purged marrow in a single institution: adverse events and incidence of secondary myelodysplasia We have analyzed the long-term outcome and toxicities in 98 patients with high-risk acute myelogenous leukemia (AML) who were treated with autologous bone marrow transplantation (ABMT) and monitored for a median observation period of 11.67 years. Between 1983 and 1994, 98 patients in our institution in first or second and higher complete remission (CR) underwent total body irradiation and high-dose cyclophosphamide prior to ABMT purged with mafosfamide. Twenty-seven out of the 90 evaluable patients (30%) were alive and in continuous CR for a median of 11.67 years (range, 6.39–15.53) after ABMT and could be considered as ‘cured’. Among the 90 patients, 39 were transplanted at first CR and had a significantly higher survival rate than those transplanted at ⩾2 CR. Younger patients (<40 years) had a better prognosis and patients with FAB M1–4 had a more favorable outcome than those with M5. Long-term complications included four patients with cardiac complications, two with renal insufficiency. Five developed HCV infections, four myelodysplastic syndrome. The incidence of cataract among the long-term survivors was 44.4%. Therefore, a significant number of adult patients with AML in first CR derived long-term benefit from ABMT, despite the risks of a few long-term complications and of MDS (4.4%).

negative: Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy. Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19. However, some of these medications have potential cardiac adverse effects. This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias. Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal. Both drugs have an anti-arrhythmic property and are proarrhythmic. The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity. Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes. Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval. This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19. The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting. The proposed protocol is taking into consideration that resources during the pandemic are limited.

negative: Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19 (1) Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak. Systemic ozone therapy (OT) could be potentially useful in the clinical management of several complications secondary to SARS-CoV-2. The rationale and mechanism of action has already been proven clinically in other viral infections and has been shown in research studies to be highly effective at decreasing organ damage mediated by inflammation and oxidative stress. This review summarizes the OT studies that illustrate the possible cytoprotective mechanism of action of ozone and its physiological by-products in target organs affected by SARS-CoV-2. (2) Methods: This review encompasses a total of 74 peer-reviewed original articles. It is mainly focused on ozone as a modulator of the NF-κB/Nrf2 pathways and IL-6/IL-1β expression. (3) Results: In experimental models and the few existent clinical studies, homeostasis of the free radical and antioxidant balance by OT was associated with a modulation of NF-κB/Nrf2 balance and IL-6 and IL-1β expression. These molecular mechanisms support the cytoprotective effects of OT against tissue damage present in many inflammatory diseases, including viral infections. (4) Conclusions: The potential cytoprotective role of OT in the management of organ damage induced by COVID-19 merits further research. Controlled clinical trials are needed.

negative: Inferring COVID-19 spreading rates and potential change points for case number forecasts As COVID-19 is rapidly spreading across the globe, short-term modeling forecasts provide time-critical information for decisions on containment and mitigation strategies. A main challenge for short-term forecasts is the assessment of key epidemiological parameters and how they change as first governmental intervention measures are showing an effect. By combining an established epidemiological model with Bayesian inference, we analyze the time dependence of the effective growth rate of new infections. For the case of COVID-19 spreading in Germany, we detect change points in the effective growth rate which correlate well with the times of publicly announced interventions.Thereby, we can (a) quantify the effects of recent governmental measures to mitigating the disease spread, and (b) incorporate analogue change points to forecast future scenarios and case numbers.Our code is freely available and can be readily adapted to any country or region.

negative: The cognitive consequences of the COVID-19 epidemic: collateral damage? Recovery from coronavirus disease 2019 (COVID-19) will be principally defined in terms of remission from respiratory symptoms, however both clinical and animal studies have shown that coronaviruses may spread to the nervous system. A systematic search on previous viral epidemics revealed that while there has been relatively little research in this area, clinical studies have commonly reported neurological disorders and cognitive difficulties. Little is known with regard to their incidence, duration or underlying neural basis. The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment, and acceleration of neurodegenerative disorders such as Alzheimer’s disease. Future knowledge of the impact of COVID-19, from epidemiological studies and clinical practice, will be needed to develop future screening and treatment programmes to minimize the long-term cognitive consequences of COVID-19.

negative: Mild COVID‐19 in a pediatric renal transplant recipient As of mid‐April 2020, the coronavirus disease of 2019 (COVID‐19) pandemic has affected more than 2 million people and caused 135,000 deaths worldwide. Not much is known about the effect of this disease in immunosuppressed children with renal transplantation (RT). Here we report a 13‐year‐old child with multiple comorbidities who acquired COVID‐19 five years post‐RT in the United States. Maintenance immunosuppression (IS) consisted of sirolimus and mycophenolate. There was no history of travel or exposure to sick contacts. The presenting features were fever, cough, rhinorrhea and hypoxemia. Diarrhea was the only extra pulmonary manifestation. Chest x‐ray was normal. He did not require intensive care unit care or ventilation. There was a transient rise in his serum creatinine without change in urine output; dialysis was not required. Slight reduction in IS was done. He had an excellent clinical recovery within four days and was able to be discharged home. His respiratory symptoms resolved but the diarrhea persisted during a 4 week follow‐up period. This report provides a brief perspective on the short‐term COVID‐19 clinical course in an immunosuppressed child. More reports will add valuable information on the potential variety of spectrum of the illness in this subset of children.

negative: Obesity: the “Achilles heel” for COVID-19?

negative: Recovery from COVID-19 Pneumonia in a Patient with Acute Severe Colitis Introduction: The coronavirus disease 2019 (COVID-19) pandemic has increased concern regarding SARS-CoV-2 infection in inflammatory bowel disease (IBD) patients, especially those on immunosuppressive therapies or with active disease. There are limited reports describing the clinical features of COVID-19 in an IBD population, and the impact of immunosuppression on the severity of the infection remains unclear. Case Report: A 33-year-old female patient with a long history of ulcerative colitis, poorly controlled, was admitted with COVID-19 a few days after being discharged from the hospital for treatment of acute severe ulcerative colitis. High-risk factors for COVID-19 complications, i.e., high-dose steroids (40 mg prednisone) and severe active disease, were present at admission. Despite the development of extensive pulmonary involvement, the patient had a favorable outcome. Discussion: Management of IBD patients during the COVID-19 pandemic has been challenging. Measures to minimize the potential risk of SARS-CoV-2 infection, including strict social distancing and self-isolation, in the IBD population have been recommended, especially for high-risk patients. Although steroid tapering and persistence of biologics are advised by professional groups, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined.

negative: Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study OBJECTIVE: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. DESIGN: Retrospective case series. SETTING: Tongji Hospital in Wuhan, China. PARTICIPANTS: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. MAIN OUTCOME MEASURES: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. RESULTS: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

negative: Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.

negative: First case of COVID-19 complicated with fulminant myocarditis: a case report and insights BACKGROUND: Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. CASE PRESENTATION: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. CONCLUSION: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

negative: Proceedings of a Consensus Conference: Pathogen Inactivation—Making Decisions About New Technologies Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.

negative: Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BACKGROUND: Angiotensin-converting enzyme-2 (ACE2) may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. DESIGN BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 32 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from vascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, troponin, B-type natriuretic peptide, N-terminal-pro hormone and D-dimer levels. SUMMARY: BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.

negative: Clearance and persistence of SARS-CoV-2 RNA in patients with COVID-19 Patients with coronavirus disease-2019 may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral clearance profile is crucial to establish a re-testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS-CoV-2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative reverse transcription-polymerase chain reaction (RT-PCR) tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT-PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than 2 weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead.

negative: The impact of the coronavirus outbreak on Macao. From tourism lockdown to tourism recovery Macao was one of the first cities outside China to start a gradual tourism lockdown in January 2020 due to the coronavirus outbreak. Although critical to Macao’s economy, tourism had essentially ceased by March 2020, as the city closed its borders to regional and foreign arrivals. This paper presents the key policy and health measures since Macao’s first coronavirus case in January. The city had recorded no coronavirus cases in the city in early March, but saw a second wave of imported coronavirus cases mostly as residents and non-resident workers returned from overseas. At the request of government, over 10% of Macao’s hotel room inventory had been allocated as quarantine hotels. The ‘top-down’ approach by government meant stringent policy measures consisting of border closures and health advisories were actioned immediately to stem the spread of coronavirus. The economic consequences to the casino industry, which supplies 85% of the government’s total tax revenues, have been dramatic, as casino revenues continue to spiral downwards by over 80% in both February and March. This paper presents Macao’s reaction to the coronavirus in a three-wave analogy. It is argued that the recovery wave should move to public-private consolidation and collaboration.

negative: A fine balance: Immunosuppression and immunotherapy in a patient with multiple sclerosis and COVID-19 Abstract Background : Treatment decisions in patients with multiple sclerosis (MS) during the coronavirus disease 2019 (COVID-19) pandemic are challenging. It is not known whether and how various disease modifying therapies, especially immunosuppressive drugs, affect COVID-19 risk and disease course. Methods : Case report Results : We report a fingolimod-treated MS patient who developed severe COVID-19 but recovered after treatment with tocilizumab. Conclusion : This report suggests that a brief course of tocilizumab for the treatment of severe COVID-19 may be effective while not aggravating pre-existing MS.

negative: MATHEMATICAL PREDICTIONS FOR COVID-19 AS A GLOBAL PANDEMIC This study shows that the disease free equilibrium (E_0 ) for COVID-19 coronavirus does not satisfy the criteria for a locally or globally asymptotic stability. This implies that as a pandemic as declared by WHO (2020) the COVID-19 coronavirus does not have a curative vaccine yet and precautionary measures are advised through quarantine and observatory procedures. Also, the Basic Reproductive number (R_0<1) by Equation (33) shows that there is a chance of decline of secondary infections when the ratio between the incidence rate in the population and the total number of infected population quarantined with observatory procedure. The effort to evaluate the disease equilibrium shows that unless there is a dedicated effort from government, decision makers and stakeholders, the world would hardly be reed of the COVID-19 coronavirus and further spread is eminent and the rate of infection will continue to increase despite the increased rate of recovery because of the absence of vaccine at the moment.

negative: Resumption of activity in gastroenterology departments. Recommendations by SEPD, AEEH, GETECCU and AEG Abstract The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: • To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. • To protect all healthcare professionals against the risks of infection with SARS-CoV-2. • To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.

negative: YouTube as a source of information on COVID-19: a pandemic of misinformation? INTRODUCTION: The COVID-19 pandemic is this century’s largest public health emergency and its successful management relies on the effective dissemination of factual information. As a social media platform with billions of daily views, YouTube has tremendous potential to both support and hinder public health efforts. However, the usefulness and accuracy of most viewed YouTube videos on COVID-19 have not been investigated. METHODS: A YouTube search was performed on 21 March 2020 using keywords ‘coronavirus’ and ‘COVID-19’, and the top 75 viewed videos from each search were analysed. Videos that were duplicates, non-English, non-audio and non-visual, exceeding 1 hour in duration, live and unrelated to COVID-19 were excluded. Two reviewers coded the source, content and characteristics of included videos. The primary outcome was usability and reliability of videos, analysed using the novel COVID-19 Specific Score (CSS), modified DISCERN (mDISCERN) and modified JAMA (mJAMA) scores. RESULTS: Of 150 videos screened, 69 (46%) were included, totalling 257 804 146 views. Nineteen (27.5%) videos contained non-factual information, totalling 62 042 609 views. Government and professional videos contained only factual information and had higher CSS than consumer videos (mean difference (MD) 2.21, 95% CI 0.10 to 4.32, p=0.037); mDISCERN scores than consumer videos (MD 2.46, 95% CI 0.50 to 4.42, p=0.008), internet news videos (MD 2.20, 95% CI 0.19 to 4.21, p=0.027) and entertainment news videos (MD 2.57, 95% CI 0.66 to 4.49, p=0.004); and mJAMA scores than entertainment news videos (MD 1.21, 95% CI 0.07 to 2.36, p=0.033) and consumer videos (MD 1.27, 95% CI 0.10 to 2.44, p=0.028). However, they only accounted for 11% of videos and 10% of views. CONCLUSION: Over one-quarter of the most viewed YouTube videos on COVID-19 contained misleading information, reaching millions of viewers worldwide. As the current COVID-19 pandemic worsens, public health agencies must better use YouTube to deliver timely and accurate information and to minimise the spread of misinformation. This may play a significant role in successfully managing the COVID-19 pandemic.

negative: Willingness to Accept Tradeoffs among Covid-19 Cases, Social-Distancing Restrictions, and Economic Impact: A Nationwide US Study We designed a discrete-choice experiment to quantify the extent to which US adults would accept greater risk of infection with SARS-CoV-2 in return for lifting social-distancing restrictions and diminishing the economic impact of the COVID-19 pandemic. 5953 adults representing all 50 states had 4 distinctly different preference patterns. About 37% were risk minimizers reluctant to accept any increases in risk of contracting the virus. Another group (26%) was primarily concerned about time required for economic recovery, accepting increases in COVID-19 risk levels up to 16% to shorten recovery from 3 to 2 years. The remaining two groups diverged on the relative importance of reopening nonessential businesses. The larger group (26%) strongly preferred delaying reopening while the smaller group (13%) would accept COVID-19 risks well beyond 20% to avoid a delay in reopening. Political affiliation, race, household income and employment status were predictive of group membership.

negative: Prediction of the time evolution of the COVID-19 disease in Guadeloupe with a stochastic evolutionary model Predictions on the time-evolution of the number of severe and critical cases of COVID-19 patients in Guadeloupe are presented. A stochastic model is purposely developed to explicitly account for the entire population (≈ 400000 inhabitants) of Guadeloupe. The available data for Guadeloupe are analysed and combined with general characteristics of the COVID-19 to constrain the parameters of the model. The time-evolution of the number of cases follows the well-known exponential-like model observed at the very beginning of a pandemic outbreak. The exponential growth of the number of infected individuals is controlled by the so-called basic reproductive number, R0, defined as the likely number of additional cases generated by a single infectious case during its infectious period TI. Because of the rather long duration of infectious period (≈ 14 days) a high rate of contamination is sustained during several weeks after the beginning of the containment period. This may constitute a source of discouragement for people restrained to respect strict containment rules. It is then unlikely that, during the containment period, R0 falls to zero. Fortunately, our models shows that the containment effects are not much sensitive to the exact value of R0 provided we have R0 < 0.6. For such conditions, we show that the number of severe and critical cases is highly tempered about 4 to 6 weeks after the beginning of the containment. Also, the maximum number of critical cases (i.e. the cases that may exceed the hospital intensive care capacity) remains near 30 when R0 < 0.6. For a larger R0 = 0.8 a slower decrease of the number of critical cases occurs, leading to a larger number of deceased patients. This last example illustrates the great importance to maintain an as low as possible R0 during and after the containment period. The rather long delay between the beginning of the containment and the appearance of the slowing-down of the rate of contamination puts a particular strength on the communication and sanitary education of people. To be mostly efficient, this communication must be done by a locally recognised medical staff. We believe that this point is a crucial matter of success.

negative: Curating evidence on mental health during COVID-19: A living systematic review

negative: Estimation of COVID-19 spread curves integrating global data and borrowing information Currently, novel coronavirus disease 2019 (COVID-19) is a big threat to global health. Rapid spread of the virus has created pandemic, and countries all over the world are struggling with a surge in COVID-19 infected cases. Scientists are working on estimating or predicting infection trajectory for the COVID-19 confirmed cases, which will be useful for future planning and policymaking to effectively cope with the disease. There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19 (on April 13, 2020): information on the disease is very limited and scattered even if it exists. This motivates the use of data integration, combining data from diverse sources and eliciting useful information with a unified view of them. In this paper, we propose a Bayesian hierarchical model that integrates global data to estimate COVID-19 infection trajectories. Due to information borrowing across multiple countries, the proposed growth curve models provide a powerful predictive tool endowed with uncertainty quantification. They outperform the existing individual country-based models. Additionally, we use countrywide covariates to adjust infection trajectories. A joint variable selection technique has been integrated into the proposed modeling scheme, which aimed to identify the possible country-level risk factors for severe disease due to COVID-19.

negative: Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 Severe coronavirus disease 2019 (COVID-19) is commonly complicated with coagulopathy, the difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2 has not been analyzed. Coagulation results and clinical features of consecutive patients with severe pneumonia induced by SARS-CoV2 (COVID group) and non-SARS-CoV2 (non-COVID group) in Tongji hospital were retrospectively analyzed and compared. Whether patients with elevated D-dimer could benefit from anticoagulant treatment was evaluated. There were 449 COVID patients and 104 non-COVID patients enrolled into the study. The 28-day mortality in COVID group was approximately twofold of mortality in non-COVID group (29.8% vs. 15.4%, P = 0.003), COVID group were older (65.1 ± 12.0 vs. 58.4 ± 18.0, years, P < 0.001) and with higher platelet count (215 ± 100 vs. 188 ± 98, ×10(9)/L, P = 0.015), comparing to non-COVID group. The 28-day mortality of heparin users were lower than nonusers In COVID group with D-dimer > 3.0 μg/mL (32.8% vs. 52.4%, P = 0.017). Patients with severe pneumonia induced by SARS-CoV2 had higher platelet count than those induced by non-SARS-CoV2, and only the former with markedly elevated D-dimer may benefit from anticoagulant treatment.

negative: Healthcare workers and H1N1 vaccination: Does having a chronic disease make a difference? Abstract Introduction A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19–3.62) times more likely than females to receive the H1N1 vaccination; the 45–54 and 55+ years old were 2.12 (95% CI 1.06–4.24) and 2.44 (95% CI 1.13–5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48–10.92). The 2 principal barriers were “fear of side effects” and “unsure of vaccine's effectiveness”. Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications. Conclusion Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.

negative: Information about the new coronavirus disease (COVID-19)

negative: Psychological and Behavioural Responses to Coronavirus Disease 2019: The Role of Personality This study examined the associations between personality traits and psychological and behavioural responses to the coronavirus disease 2019 (COVID‐19) pandemic. Personality was assessed in January/February 2020 when the public was not aware of the spread of coronavirus in the USA. Participants were reassessed in late March 2020 with four sets of questions about the pandemic: concerns, precautions, preparatory behaviours, and duration estimates. The sample consisted of N = 2066 participants (mean age = 51.42; range = 18–98; 48.5% women). Regression models were used to analyse the data with age, gender, education, race, and ethnicity as covariates. Consistent with the preregistered hypotheses, higher neuroticism was related to more concerns and longer duration estimates related to COVID‐19, higher extraversion was related to shorter duration estimates, and higher conscientiousness was associated with more precautions. In contrast to the preregistered hypotheses, higher neuroticism was associated with fewer precautions and unrelated to preparatory behaviours. Age moderated several trait–response associations, suggesting that some of the responses were associated more strongly in older adults, a group at risk for complications of COVID‐19. For example, older adults high in conscientiousness prepared more. The present findings provide insights into how personality predicts concerns and behaviours related to the COVID‐19 pandemic. © 2020 European Association of Personality Psychology

negative: The Novel Coronavirus Disease (COVID-19) Threat for Patients with Cardiovascular Disease and Cancer

negative: Nuevo coronavirus (2019-nCov): ¿tiene suficientes unidades de cuidados intensivos?

negative: Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients Background: Viral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Suboptimal T and B cell responses can delay viral clearance in MERS and SARS patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined.Methods: From January 26 to February 28, 2020, an observational study was launched at Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. We comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. Findings: In 25 enrolled COVID-19 patients, lymphopeniawas a common feature. After the treatment, 14 patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cellsand B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. Conclusions: By comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidanceas a criterion for releasing and discharging patients.

negative: Clinical Manifestations The incubation period after infection of Influenza A(H1N1) is usually 1–7 days, being longer than common influenza and bird flu.

negative: Coronavirus Disease (COVID-19): Implications for Cardiovascular and Socially At-risk Populations Dennison Himmelfarb and Baptiste discuss the implications of coronavirus disease (COVID-19) for cardiovascular and socially at-risk populations COVID-19 is an infectious respiratory disease caused by the newly discovered pathogen, SARS-CoV-2, a novel RNA-dependent RNA polymerase betacoronavirus that is thought to derive from bats At this time, there are no specific vaccines or treatments for COVID-19 The best way to prevent and slow transmission is to be well informed about the COVID-19 virus, the disease it causes, and how it spreads

negative: Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression The current outbreak of Coronavirus Disease 2019 (COVID-19) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID-19 pneumonia. This is a 52-year-old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non-transplanted COVID-19 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone-based therapy, the COVID-19 pneumonia in this long-term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID-19 pneumonia.

negative: Emerging infectious diseases and outbreaks: implications for women’s reproductive health and rights in resource-poor settings This century is witnessing dramatic changes in the health needs of the world’s populations. The double burden of infectious and chronic diseases constitutes major causes of morbidity and mortality. Over the last two decades, there has been a rise in infectious diseases, including the severe acute respiratory syndrome virus (SARS), the H1N1 pandemic influenza, the Ebolavirus and the Covid-19 virus. These diseases have rapidly spread across the world and have reminded us of the unprecedented connectivity that defines our modern civilization. Though some countries have made substantial progress toward improving global surveillance for emerging infectious diseases (EIDs), the vast majority of Low-and Middle-income Countries (LMICs) with fragile health systems and various system-related bottlenecks remain vulnerable to outbreaks and, as such, experience dramatic social and economic consequences when they are reported. Lessons learned from past outbreaks suggest that gender inequalities are common across a range of health issues relating to Sexual and Reproductive Health and Rights (SRHR), with women being particularly disadvantaged, partially due to the burden placed on them. Though these countries are striving to improve their health systems and be more inclusive to this vulnerable group, the national/ global outbreaks have burdened the overall system and thus paralyzed normal services dedicated to the delivery of Sexual and Reproductive Health (SRH) services. In this paper, we discuss the global commitments to SRH, the impact of the EIDs on the LMICs, the failure in the delivery of SRH services, and the strategies for successful implementation of recovery plans that must address the specific and differentiated needs of women and girls in resource-poor settings.

negative: The local stability of a modified multi-strain SIR model for emerging viral strains We study a novel multi-strain SIR epidemic model with selective immunity by vaccination. A newer strain is made to emerge in the population when a preexisting strain has reached equilibrium. We assume that this newer strain does not exhibit cross-immunity with the original strain, hence those who are vaccinated and recovered from the original strain become susceptible to the newer strain. Recent events involving the COVID-19 virus demonstrates that it is possible for a viral strain to emerge from a population at a time when the influenza virus, a well-known virus with a vaccine readily available for some of its strains, is active in a population. We solved for four different equilibrium points and investigated the conditions for existence and local stability. The reproduction number was also determined for the epidemiological model and found to be consistent with the local stability condition for the disease-free equilibrium.

negative: Suicide prevention during the COVID-19 outbreak

negative: COVID-19 and emerging viral infections: The case for interferon lambda With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.

negative: How many are at increased risk of severe COVID-19 disease? Rapid global, regional and national estimates for 2020 Background The risk of severe COVID-19 disease is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 illness, and how this varies between countries may inform the design of possible strategies to shield those at highest risk. Methods We estimated the number of individuals at increased risk of severe COVID-19 disease by age (5-year age groups), sex and country (n=188) based on prevalence data from the Global Burden of Disease (GBD) study for 2017 and United Nations population estimates for 2020. We also calculated the number of individuals without an underlying condition that could be considered at-risk because of their age, using thresholds from 50-70 years. The list of underlying conditions relevant to COVID-19 disease was determined by mapping conditions listed in GBD to the guidelines published by WHO and public health agencies in the UK and US. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. Results We estimate that 1.7 (1.0 - 2.4) billion individuals (22% [15-28%] of the global population) are at increased risk of severe COVID-19 disease. The share of the population at increased risk ranges from 16% in Africa to 31% in Europe. Chronic kidney disease (CKD), cardiovascular disease (CVD), diabetes and chronic respiratory disease (CRD) were the most prevalent conditions in males and females aged 50+ years. African countries with a high prevalence of HIV/AIDS and Island countries with a high prevalence of diabetes, also had a high share of the population at increased risk. The prevalence of multimorbidity (>1 underlying conditions) was three times higher in Europe than in Africa (10% vs 3%). Conclusion Based on current guidelines and prevalence data from GBD, we estimate that one in five individuals worldwide has a condition that is on the list of those at increased risk of severe COVID-19 disease. However, for many of these individuals the underlying condition will be undiagnosed or not severe enough to be captured in health systems, and in some cases the increase in risk may be quite modest. There is an urgent need for robust analyses of the risks associated with different underlying conditions so that countries can identify the highest risk groups and develop targeted shielding policies to mitigate the effects of the COVID-19 pandemic.

negative: Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China Background: The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference. Methods: From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). Results: This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20–24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (p < 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (p < 0.05). Conclusions: During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.

negative: Pandemic related Health literacy - A Systematic Review of literature in COVID-19, SARS and MERS pandemics Background: Health literacy plays an essential role in ones ability to acquire and understand critical medical information in the COVID-19 infodemic and other pandemics. Purpose: To summarize the assessment, levels and determinants of pandemic related health literacy and its associated clinical outcomes. Data sources: Medline, Embase, PsychINFO, CINAHL, arXiv, bioRxiv, medRxiv, and Social Science Research Network. The start date was unrestricted and current as of 22 April 2020. Study selection Studies which evaluated health literacy related to novel coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) Data extraction Data on the characteristics of study designs, instruments, participants and level of health literacy were collected. Items used in instruments were grouped under the themes of knowledge, attitudes and practices. Determinants of health literacy were grouped into five domains (socio-demographic, medical, psychological/psychiatric, health systems related and others). Data synthesis: Of 2,065 articles screened, 70 articles were included. 21, 17 and 32 studies evaluated health literacy related to COVID-19, SARS and MERS, respectively. The rates of low pandemic health literacy ranged from 4.3 to 57.9% among medical-related populations and 4.0% to 82.5% among non-medical populations. Knowledge about symptoms and transmission of infection; worry about infection and, practices related to mask usage and hand hygiene was most frequently evaluated. Socio-demographic determinants of health literacy were most studied, where higher education level, older age and female gender were associated with better health literacy. No studies evaluated outcomes associated with health literacy. Limitations Non-English articles were excluded. Conclusion: The level of pandemic related health literacy is sub-optimal. Healthcare administrators need to be aware of health literacy determinants when formulating policies in pandemics.

negative: Coronavirus Disease 2019 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm?

negative: Characteristics, Treatment Outcomes and Role of Hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study Purpose: The present study was undertaken to investigate epidemiological distribution, clinical manifestation, co morbid status, treatment strategy and case fatality index of emerging COVID-19 infection at SMS Medical College Hospital, Jaipur, Rajasthan. It also evaluated efficacy of hydroxychloroquine (HCQ) in treatment of patients and risk of serious adverse outcomes in patients with COVID-19 in relation to their co morbid status. Materials and methods: In an attempt to provide extensive information pertaining to epidemiological and clinical characteristics of COVID-19, the present study was undertaken on 522 patients. The patients were COVID-19 confirmed positive by genomic analysis through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at SMS Medical College and Attached Hospitals, Jaipur. The indoor admitted patient's information inclusive of demographic profile (age, sex, nationality, residence), date of confirmation for positive COVID-19 case, travel/ exposure history, date of recovery/ death, clinical features, co morbidities and treatment plan was recorded. A serial follow-up of recovered patients to evaluate infective period of the disease was also part of the study. Results: A total of 522 patients of laboratory confirmed COVID-19 test by RT-PCR at SMS Hospitals, Jaipur were assessed. Among the confirmed cases, most of patients were young adult in the age group with mean age of 35.42 years. 22.41% patients were below 20 years of age, majority of patients (58.80%) were in the age range of 21 to 50 years and only 18.79% patient population was in the age range of above 50 years. Females (39.08%) were affected less than males (60.91%) with an average sex ratio of female: male being 0.64. Out of the total analyzed patients, only 24.32% patients were symptomatic, among them fever (55.90%), cough (52.75%), sore throat (49.60%) and shortness of breath (46.45%) were the most common presenting clinical manifestations while a few patients also had symptoms of headache (26.77%), chest pain (6.29%) and other symptoms (7.87%) like pain abdomen, fatigue, joints pain, altered sensorium etc. Most of symptomatic patients belonging to older age group. An average of 40.40% patient population of above 50 years of age, were symptomatic while none of the patients below 10 years of age were symptomatic. 13.98% patients had some or the other underlying co morbid disease. The most prevalent co morbidity was hypertension (42.46%) followed by Diabetes mellitus (39.72%), Old k-chest (20.54%), COPD/ Bronchial Asthma (16.43%), Coronary artery disease (13.69%), Chronic kidney disease (13.69%) and Valvular heart disease (6.84%) distributed in co morbid patients of COVID-19. 60.27% of patient population with underlying co morbid conditions were more prone to develop symptomatology complex as compared to that observed in patients with no co morbidity (18.42%). 116 patients had recovered with effective treatment till the date of data analysis. Time of recovery was counted from the date of positive report to 1st negative report of oropharyngeal sample by RT-PCR for COVID-19 with an average recovery time of 8.15 days. 23.27% patients recovered within 5 days, while 52.58% patients took about 6-10 days, 23.27% patients took 11-15 days and remaining 0.86% took more than 16 days to recover. In the present study 15 patients had died till analysis of data, among the deceased, 73.33% were above 50 year of age with a male preponderance (66.6%). Interestingly, all deceased (100%) had presented with clinical manifestations of COVID-19 and all had underlying multiple co morbid conditions. Majority of patients had early mortality after admission to hospital with two third death account in initial three days. Asymptomatic patients (cases) treated with HCQ recovered early (average recovery time =5.4 days) compared to asymptomatic patients who did not receive any treatment (control group) and had longer recovery time (average recovery time =7.6 days). Conclusion: The varied spectra of COVID-19 mostly affects young adult age group (third to fifth decades of life). Interestingly, early age group was also affected in significant proportion when compared with similar data from other countries. It was observed that male population seemed to be was more prone to getting infected. Majority of COVID-19 positive patients (nearly three-fourth) were asymptomatic (mostly in young age range) at the time of diagnosis, which poses a major challenge for health care workers. Fever, cough, sore throat and shortness of breath were major symptoms that could be detected in such COVID-19 patients. Symptomatic clinical manifestations were more common in old age population. Infectivity was higher in patients that had underlying co morbid disease, especially in patients with multiple co morbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease. Average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and co morbid patients as compared to other similarly matched group. Most of mortality was noted within first few days of admission, suggestive of early mortality due to the primary disease process. Treatment with HCQ had early recovery without effectively influencing the overall mortality.

negative: Macrophage activation syndrome in a patient with axial spondyloarthritis on adalimumab Macrophage activation syndrome (MAS) is a rare and potentially fatal condition characterized by excessive activation and uncontrolled proliferation of T lymphocytes and macrophages, leading to overwhelming systemic inflammation and cytokine release. MAS has been reported with viral infections, autoimmune disorders, malignancies, and medications. We describe a case of a patient with axial spondyloarthritis (axSpA) treated with adalimumab, who presented with MAS.

negative: New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? ABSTRACT Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonary infection in humans. The efforts of international health authorities have since focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the most severe effects of the disease. In the absence of a known efficient therapy and because of the situation of a public-health emergency, it made sense to investigate the possible effect of chloroquine/hydroxychloroquine against SARS-CoV-2 since this molecule was previously described as a potent inhibitor of most coronaviruses, including SARS-CoV-1. Preliminary trials of chloroquine repurposing in the treatment of COVID-19 in China have been encouraging, leading to several new trials. Here we discuss the possible mechanisms of chloroquine interference with the SARS-CoV-2 replication cycle.

negative: Early recovery following new onset anosmia during the COVID-19 pandemic – an observational cohort study BACKGROUND: A rapidly evolving evidence suggests that smell and taste disturbance are common symptoms in COVID-19 infection. As yet there are no reports on duration and recovery rates. We set out to characterise patients reporting new onset smell and taste disturbance during the COVID-19 pandemic and report on early recovery rates. METHODS: Online Survey of patients reporting self-diagnosed new onset smell and taste disturbance during the COVID-19 pandemic, with 1 week follow-up. RESULTS: Three hundred eighty-two patents completed bot an initial and follow-up survey. 86.4% reported complete anosmia and a further 11.5% a very severe loss of smell at the time of completing the first survey. At follow-up 1 week later, there is already significant improvement in self-rating of severity of olfactory loss. 80.1% report lower severity scores at follow-up, 17.6% are unchanged and 1.9% are worse. 11.5% already report compete resolution at follow up, while 17.3% report persistent complete loss of smell, with reported duration being 1 to over 4 weeks. This is reflected in the overall cumulative improvement rate of 79% patients overall in the interval between surveys. CONCLUSIONS: A review of the growing evidence base supports the likelihood that out cohort have suffered olfactory loss as part of COVID-19 infection. While early recovery rates are encouraging, long term rates will need to be further investigated and there may be an increase in patients with persistent post-viral loss as a result of the pandemic. We further call for loss of sense of smell to be formerly recognised as a marker of COVID-19 infection.

negative: The effect of COVID-19 on global population and its fatality rate: Retrospective study by online database OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a current new virulent disease rising its transmission and fatality with each passing day in the worldwide population. COVID-19 is emerged as a respiratory infection and a suspicious origin of animals and transmission to human in Wuhan, China on December 2019. Later this, the virus was transmitted from person to person through droplets and contacts. The World Health Organization, Centers for Disease Control and Prevention, and the National Health Commission of the People’s Republic of China have taken immediate action to reduce transmission and fatality associated with COVID-19 as minimum as possible. However, action has failed to stop transmission of COVID-19 from China to other countries. Since there was no chain break of the virus, the chances are more to increase the case number and fatality. Hence, the study has been designed to perceive the current effect of COVID-19 on the global population and its fatality. The study also focused on review related to treatment for COVID-19. MATERIAL AND METHODS: Online database of epidemic disease COVID-19 cases number was collected from www.channelnewsasia.com on 7(th) April 2020. This data was used to observe the past and present circumstances in the global population and its fatality. The effect of treatment on COVID-19 was reviewed from the few databases of clinical trials (antiviral and antibacterial drugs). RESULTS: The online data are used to observe a significant increase ratio of COVID-19 cases and its fatality rate in worldwide as well as country wise. The COVID-19 cases are high in the United States (27.5%), whereas the fatality rate is high in Italy (12.47%). The prevalence of COVID-19 is expected to be reaching 4 million by the end of April 2020 and the fatality rate also might be reached high. CONCLUSION: We have come to the conclusion that the effect of COVID-19 on the global population is significantly increased and the fatality rate also elevated (2.48% to 5.52%). The hydroxychloroquine-azithromycin combination treatment has shown significant improvement in patients with COVID-19 compared to treat with other drugs.

negative: COVID-19: Long-term Planning for Procedure-based Specialties During Extended Mitigation and Suppression Strategies

negative: The effectiveness of quarantine of Wuhan city against the Corona Virus Disease 2019 (COVID-19): A well-mixed SEIR model analysis A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed "susceptible exposed infectious recovered" (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6-18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of COVID-19 infections and delay the time of peak infection.

negative: What are We Depressed about When We Talk about COVID19: Mental Health Analysis on Tweets Using Natural Language Processing The outbreak of coronavirus disease 2019 (COVID-19) recently has affected human life to a great extent. Besides direct physical and economic threats, the pandemic also indirectly impact people's mental health conditions, which can be overwhelming but difficult to measure. The problem may come from various reasons such as unemployment status, stay-at-home policy, fear for the virus, and so forth. In this work, we focus on applying natural language processing (NLP) techniques to analyze tweets in terms of mental health. We trained deep models that classify each tweet into the following emotions: anger, anticipation, disgust, fear, joy, sadness, surprise and trust. We build the EmoCT (Emotion-Covid19-Tweet) dataset for the training purpose by manually labeling 1,000 English tweets. Furthermore, we propose and compare two methods to find out the reasons that are causing sadness and fear.

negative: Cardiovascular Disease and Surgery Amid COVID-19 Pandemic

negative: ELSA recommendations for minimally invasive surgery during a community spread pandemic: a centered approach in Asia from widespread to recovery phases BACKGROUND: The COVID-19 pandemic has resulted in significant changes to surgical practice across the worlds. Some countries are seeing a tailing down of cases, while others are still having persistent and sustained community spread. These evolving disease patterns call for a customized and dynamic approach to the selection, screening, planning, and for the conduct of surgery for these patients. METHODS: The current literature and various international society guidelines were reviewed and a set of recommendations were drafted. These were circulated to the Governors of the Endoscopic and Laparoscopic Surgeons of Asia (ELSA) for expert comments and discussion. The results of these were compiled and are presented in this paper. RESULTS: The recommendations include guidance for selection and screening of patients in times of active community spread, limited community spread, during times of sporadic cases or recovery and the transition between phases. Personal protective equipment requirements are also reviewed for each phase as minimum requirements. Capability management for the re-opening of services is also discussed. The choice between open and laparoscopic surgery is patient based, and the relative advantages of laparoscopic surgery with regard to complications, and respiratory recovery after major surgery has to be weighed against the lack of safety data for laparoscopic surgery in COVID-19 positive patients. We provide recommendations on the operating room set up and conduct of general surgery. If laparoscopic surgery is to be performed, we describe circuit modifications to assist in reducing plume generation and aerosolization. CONCLUSION: The COVID-19 pandemic requires every surgical unit to have clear guidelines to ensure both patient and staff safety. These guidelines may assist in providing guidance to units developing their own protocols. A judicious approach must be adopted as surgical units look to re-open services as the pandemic evolves.

negative: COVID-19 patients for tracheostomy: Anesthetic and team considerations

negative: Remdesivir in treatment of COVID-19: A systematic benefit-risk assessment Background: There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to strengthen the ongoing understanding of the benefit-risk balance for remdesivir in COVID-19 treatment by using a structured method which uses all available data. Methods: The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared to standard of care, placebo or other treatments. We searched PubMed,Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results: Several key benefits and risks for use of remdesivir in COVID-19 compared to placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR=1.23, 95% CI: 0.87, 1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) comparted to the placebo group (26%), however more patients in the remdesivir group discontinued treatment as a result of an adverse event compared to those patients receiving placebo (12% vs 5%). Conclusions: Preliminary clinical trial results suggest a favourable benefit-risk profile for remdesivir compared to placebo, however there is limited safety data available at the current time. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.

negative: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection Summary Background The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. Methods We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). Findings We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. Interpretation Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations. Published online May 9, 2003 http://image.thelancet.com/extras/03art4454web.pdf

negative: Practical Steps to Improve Air Flow in Long-Term Care Resident Rooms to Reduce COVID-19 Infection Risk Abstract The potential for spread of COVID-19 infections in Skilled Nursing Facilities and other Long-Term Care sites poses new challenges for Nursing Home Administrators to protect patients and staff. It is anticipated that as Acute Care Hospitals reach capacity, Nursing Homes may retain COVID-19 infected residents longer prior to transferring to an Acute Care Hospital. This article outlines 5 pragmatic steps that Long-Term Care facilities can take to manage airflow within resident rooms to reduce the potential for spread of infectious airborne droplets into surrounding areas including hallways and adjacent rooms, using strategies adapted from negative pressure isolation rooms in acute care facilities.

negative: NSAIDs in patients with viral infections, including Covid-19: victims or perpetrators? Abstract Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.

negative: Reversal of Infected Host Gene Expression Identifies Repurposed Drug Candidates for COVID-19 Repurposing existing drugs is a timely option to cope with COVID-19. We predicted therapeutic candidates that could reverse the gene expression of coronavirus-infected host cells. Thirteen expression signatures computed from various experimental conditions and preclinical models could be reversed by those compounds known to be effective against SARS- or MERS-CoV, as well as the drug candidates recently shown to be effective against SARS-CoV-2. We selected ten novel candidates to further evaluate their in vitro efficacy against SARS-CoV-2 infection. Four compounds bortezomib, dactolisib, alvocidib and methotrexate inhibited the formation of virus infection-induced cytopathic effect in Vero E6 cells at 1 μM, yet such a concentration seems toxic to the cells as well. While the evaluation in other permissive cells and the prediction of toxicity are needed to optimize and minimize their antiviral activity and cytotoxicity, respectively, this computational approach has the potential to rapidly and rationally identify drug candidates against COVID-19.

negative: SEROEPIDEMIOLOGIC STUDIES OF CORONAVIRUS INFECTION IN ADULTS AND CHILDREN(1) McIntosh, K. A. Z. Kapikian, H. C Turner, J. W. Hartley, R. H. Parrott and R. M. Chanock. (Lab. of Infectious Diseases, NIAID, NIH, Bethesda, Md. 20014) Sero-epidemiologic studies of coronavirus infection in adults and children. Amer. J. Epid., 1970, 97: 585–592-A seroepidemiologic study of infection by coronavirus strains 229E, OC38, OC43, and mouse hepatitis virus (MHV) strain A-59, is described. In adults with upper respiratory disease, two “outbreaks” of coronavirus infection occurred, one during the winter of 1965–1966 associated with complement fixing (CF) antibody responses to OC38, OC43 and MHV, and the other during the following winter associated with CF antibody responses to 229E. In hospitalized children, infection with 229E was rare; infection with OC38, OC43, and MHV occurred less often in hospitalized children with lower respiratory tract disease (3.5%) than in a control group with non-respiratory tract disease (8.2%). The limitations of the CF test using available coronavirus antigens are discussed.

negative: A current review of COVID-19 for the cardiovascular specialist Abstract Although Coronavirus Disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include 1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; 2) acute coronary syndrome due to acute atherothrombosis in a virally-induced thrombotic and inflammatory milieu; 3) microvascular dysfunction due to diffuse microthrombi or vascular injury; 4) stress-related cardiomyopathy (Takotsubo syndrome); 5) non-ischemic myocardial injury due to a hyperinflammatory cytokine storm; or 6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, d-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative non-ischemic causes of injury, integrating the level of suspicion for COVID-19.

negative: Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.

negative: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

negative: Mathematical modeling of the spread of the coronavirus disease 2019 (COVID-19) taking into account the undetected infections. The case of China Abstract In this paper we develop a mathematical model for the spread of the coronavirus disease 2019 (COVID-19). It is a new θ-SEIHRD model (not a SIR, SEIR or other general purpose model), which takes into account the known special characteristics of this disease, as the existence of infectious undetected cases and the different sanitary and infectiousness conditions of hospitalized people. In particular, it includes a novel approach that considers the fraction θ of detected cases over the real total infected cases, which allows to study the importance of this ratio on the impact of COVID-19. The model is also able to estimate the needs of beds in hospitals. It is complex enough to capture the most important effects, but also simple enough to allow an affordable identification of its parameters, using the data that authorities report on this pandemic. We study the particular case of China (including Chinese Mainland, Macao, Hong-Kong and Taiwan, as done by the World Health Organization in its reports on COVID-19), the country spreading the disease, and use its reported data to identify the model parameters, which can be of interest for estimating the spread of COVID-19 in other countries. We show a good agreement between the reported data and the estimations given by our model. We also study the behavior of the outputs returned by our model when considering incomplete reported data (by truncating them at some dates before and after the peak of daily reported cases). By comparing those results, we can estimate the error produced by the model when identifying the parameters at early stages of the pandemic. Finally, taking into account the advantages of the novelties introduced by our model, we study different scenarios to show how different values of the percentage of detected cases would have changed the global magnitude of COVID-19 in China, which can be of interest for policy makers.

negative: Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

negative: Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016) This article lists the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2016. Changes to virus taxonomy (the Universal Scheme of Virus Classification of the International Committee on Taxonomy of Viruses [ICTV]) now take place annually and are the result of a multi-stage process. In accordance with the ICTV Statutes (http://www.ictvonline.org/statutes.asp), proposals submitted to the ICTV Executive Committee (EC) undergo a review process that involves input from the ICTV Study Groups (SGs) and Subcommittees (SCs), other interested virologists, and the EC. After final approval by the EC, proposals are then presented for ratification to the full ICTV membership by publication on an ICTV web site (http://www.ictvonline.org/) followed by an electronic vote. The latest set of proposals approved by the EC was made available on the ICTV website by January 2016 (https://talk.ictvonline.org/files/proposals/). A list of these proposals was then emailed on 28 March 2016 to the 148 members of ICTV, namely the EC Members, Life Members, ICTV Subcommittee Members (including the SG chairs) and ICTV National Representatives. Members were then requested to vote on whether to ratify the taxonomic proposals (voting closed on 29 April 2016).

negative: Intervention Serology and Interaction Substitution: Modeling the Role of ‘Shield Immunity’ in Reducing COVID-19 Epidemic Spread The COVID-19 pandemic has precipitated a global crisis, with more than 690,000 confirmed cases and more than 33,000 confirmed deaths globally as of March 30, 2020 [1–4]. At present twOfficentral public health control strategies have emerged: mitigation and suppression (e.g, [5]). Both strategies focus on reducing new infections by reducing interactions (and both raise questions of sustainability and long-term tactics). Complementary to those approaches, here we develop and analyze an epidemiological intervention model that leverages serological tests [6, 7] to identify and deploy recovered individuals as focal points for sustaining safer interactions via interaction substitution, i.e., to develop what we term ‘shield immunity’ at the population scale. Recovered individuals, in the present context, represent those who have developed protective, antibodies to SARS-CoV-2 and are no longer shedding virus [8]. The objective of a shield immunity strategy is to help sustain the interactions necessary for the functioning of essential goods and services (including but not limited to tending to the elderly [9], hospital care, schools, and food supply) while decreasing the probability of transmission during such essential interactions. We show that a shield immunity approach may significantly reduce the length and reduce the overall burden of an outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well recognized roles in estimating prevalence [10, 11] and in the potential development of plasma-based therapies [12–15].

negative: Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak Abstract Backgrounds An ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city in China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and other countries. We present estimates of the basic reproduction number, R 0, of 2019-nCoV in the early phase of the outbreak. Methods Accounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate (γ), we estimated R 0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI. Findings The early outbreak data largely follows the exponential growth. We estimated that the mean R 0 ranges from 2.24 (95%CI: 1.96–2.55) to 3.58 (95%CI: 2.89–4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R 0. Conclusion The mean estimate of R 0 for the 2019-nCoV ranges from 2.24 to 3.58, and is significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.

negative: Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records BACKGROUND: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. METHODS: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. FINDINGS: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. INTERPRETATION: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. FUNDING: Hubei Science and Technology Plan, Wuhan University Medical Development Plan.

negative: Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study BACKGROUND: The role of site of infection in sepsis has been poorly characterized. Additionally, sepsis epidemiology has evolved. Early mortality has decreased, but many survivors now progress into chronic critical illness (CCI). This study sought to determine if there were significant differences in the host response and current epidemiology of surgical sepsis categorized by site of infection. STUDY DESIGN: This is a longitudinal study of surgical sepsis patients characterized by baseline predisposition, insult characteristics, serial biomarkers, hospital outcomes, and long-term outcomes. Patients were categorized into five anatomic sites of infection. RESULTS: The 316 study patients were predominantly Caucasian; half were male, with a mean age of 62 years, high comorbidity burden, and low 30-day mortality (10%). The primary sites were abdominal (44%), pulmonary (19%), skin/soft tissue (S/ST, 17%), genitourinary (GU, 12%), and vascular (7%). Most abdominal infections were present on admission and required source control. Comparatively, they had more prolonged proinflammation, immunosuppression, and persistent organ dysfunction. Their long-term outcome was poor with 37% CCI (defined as > 14 in ICU with organ dysfunction), 49% poor discharge dispositions, and 30% 1-year mortality. Most pulmonary infections were hospital-acquired pneumonia. They had similar protracted proinflammation and organ dysfunction, but immunosuppression normalized. Long-term outcomes are similarly poor (54% CCI, 47% poor disposition, 32% 1-year mortality). S/ST and GU infections occurred in younger patients with fewer comorbidities, less perturbed immune responses, and faster resolution of organ dysfunction. Comparatively, S/ST had better long-term outcomes (23% CCI, 39% poor disposition, 13% 1-year mortality) and GU had the best (10% CCI, 20% poor disposition, 10% 1-year mortality). Vascular sepsis patients were older males, with more comorbidities. Proinflammation was blunted with baseline immunosuppression and organ dysfunction that persisted. They had the worst long-term outcomes (38% CCI, 67% poor disposition, 57% 1-year mortality). CONCLUSION: There are notable differences in baseline predisposition, host responses, and clinical outcomes by site of infection in surgical sepsis. While previous studies have focused on differences in hospital mortality, this study provides unique insights into the host response and long-term outcomes associated with different sites of infection.

negative: Perspectives of Immune Therapy in Coronavirus Disease 2019 The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.

negative: Analysis of 92 deceased patients with COVID-19 OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION: The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.

negative: Comparison of the Indicators of Psychological Stress in the Population of Hubei Province and Non-Endemic Provinces in China During Two Weeks During the Coronavirus Disease 2019 (COVID-19) Outbreak in February 2020 BACKGROUND: During February 2020, the coronavirus disease 2019 (COVID-19) epidemic in Hubei Province, China, was at its height, requiring isolation of the population. This study aimed to compare the emotional state, somatic responses, sleep quality, and behavior of people in Hubei Province with non-endemic provinces in China during two weeks in February 2020. MATERIAL/METHODS: Questionnaires were completed by 939 individuals (357 men; 582 women), including 33 from Hubei and 906 from non-endemic provinces. The Stress Response Questionnaire (SRQ) determined the emotional state, somatic responses, and behavior. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the duration of sleep and sleep quality. RESULTS: There were 939 study participants, aged 18–24 years (35.89%) and 25–39 years (35.57%); 65.92% were university students. During a two week period in February 2020, the emotional state and behavior of participants in Hubei improved, but the quality of sleep did not. Health workers and business people became increasingly anxious, but other professionals became less anxious. The data showed that most people in Hubei Province developed a more positive attitude regarding their risk of infection and the chances of surviving the COVID-19 epidemic. CONCLUSIONS: During a two-week period, front-line health workers and people in Hubei Province became less anxious about the COVID-19 epidemic, but sleep quality did not improve. Despite public awareness, levels of anxiety exist that affect the quality of life during epidemics, including periods of population quarantine. Therefore, health education should be combined with psychological counseling for vulnerable individuals.

negative: Serological evidence of coronavirus infections in native hamadryas baboons (Papio hamadryas hamadryas) of the Kingdom of Saudi Arabia The hamadryas baboon (Papio hamadryas hamadryas) is the only indigenous species of non-human primates (NHP) found in the Kingdom of Saudi Arabia (KSA). There are no peer-reviewed publications on viral infections of the baboons of KSA. Apart from camels, other animals are likely sources of the novel Middle East Respiratory Syndrome coronavirus (MERSCoV) for humans. We investigated evidence of highly pathogenic coronavirus infections including MERSCoV in a large group of commensal baboons accompanied by feral dogs, on the outskirts of Ta'if city, KSA, in February 2013. Fifty baboons (16 juveniles and 34 adults) were screened for serum antibodies to human coronaviruses (HCoV-043/-NL63/-229) and canine coronaviruses (CCoV-1-3) using direct Enzyme-linked Immunosorbent Assay (ELISA) technique and for MERSCoV antibodies using Serum Neutralization Test (SNT). Of the 50 sampled baboons, 22% (n = 11) were seropositive to HCoVs, 10% (n = 5) were seropositive to CCoVs, while none had detectable MERSCoV antibodies. These findings bear potentially significant implications for public health, canine health and baboon conservation efforts, necessitating follow-up investigations and preventive measures at locations where baboons frequent human habitations, or are regarded as tourist attractions, in KSA.

negative: Modeling and prediction of COVID-19 pandemic using Gaussian mixture model COVID-19 is caused by a novel coronavirus and has played havoc on many countries across the globe. A majority of the world population is now living in a restricted environment for more than a month with minimal economic activities, to prevent exposure to this highly infectious disease. Medical professionals are going through a stressful period while trying to save the larger population. In this paper, we develop two different models to capture the trend of a number of cases and also predict the cases in the days to come, so that appropriate preparations can be made to fight this disease. The first one is a mathematical model accounting for various parameters relating to the spread of the virus, while the second one is a non-parametric model based on the Fourier decomposition method (FDM), fitted on the available data. The study is performed for various countries, but detailed results are provided for the India, Italy, and United States of America (USA). The turnaround dates for the trend of infected cases are estimated. The end-dates are also predicted and are found to agree well with a very popular study based on the classic susceptible-infected-recovered (SIR) model. Worldwide, the total number of expected cases and deaths are 12.7 × 10(6) and 5.27 × 10(5), respectively, predicted with data as of 06-06-2020 and 95% confidence intervals. The proposed study produces promising results with the potential to serve as a good complement to existing methods for continuous predictive monitoring of the COVID-19 pandemic.

negative: Salvage use of tissue plasminogen activator (tPA) in the setting of acute respiratory distress syndrome (ARDS) due to COVID-19 in the USA: a Markov decision analysis BACKGROUND: COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO2/FiO2 (mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic. METHODS: A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO2/FiO2 of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature. RESULTS: The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios. CONCLUSIONS: Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.

negative: Neurological manifestations and neuro‐invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2 INTRODUCTION: Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID‐19 and possible neuro‐invasive mechanisms of Sars‐CoV‐2. METHODS: Pubmed, WebOfScience and Covid‐dedicated databases were searched for the combination of COVID‐19 terminology and neurology terminology up to May 10(th) 2020. Social media channels were followed‐up between March 15(th) and May 10(th) 2020 for postings with the same scope. Neurological manifestations were extracted from the identified manuscripts and combined to provide a useful summary for the neurologist in clinical practice. RESULTS: Neurological manifestations potentially related to COVID‐19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and auto‐immune disorders such as Guillain‐Barré Syndrome often present in patients with more severe COVID‐19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild‐to‐moderate COVID‐19 even without associated nasal symptoms and often present in an early stage of the disease. CONCLUSION: Physicians should be aware of the neurological manifestations in patients with COVID‐19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID‐19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long‐term consequences of the infection on human health remain uncertain especially with regards to the neurological system.

negative: Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

negative: Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome. The aim of this study was to investigate pulmonary function and exercise capacity in a group of survivors of the severe acute respiratory syndrome (SARS). At 3 months after hospital discharge, 46 survivors of SARS underwent the following evaluation: spirometry, static lung volumes and carbon monoxide transfer factor (TL,CO). In total, 44 of these patients underwent cardiopulmonary exercise testing. No abnormalities were detected in the pulmonary function tests in 23 (50%) of the patients. Abnormalities of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and TL,CO were detected in seven (15%), 12 (26%), one (2%) and 18 (39%) patients, respectively. All of these abnormalities were mild except in one case. In 18 patients (41%), the maximum aerobic capacity was below the lower limit of the normal range. Breathing reserve was low in four patients and significant oxygen desaturation was detected in a further four patients. Comparison of the measured exercise capacity with resting pulmonary function tests showed many cases of discordance in impairment. In conclusion, pulmonary function defects were detected in half of the recovered severe acute respiratory syndrome patients 3 months after hospital discharge, but the impairment was mild in almost all cases. Many patients had reduced exercise capacity that cannot be accounted for by impairment of pulmonary function.

negative: Characterization of clinical progression of COVID-19 patients in Shenzhen, China The COVID-19 pandemic has stressed healthcare care systems throughout the world. Understanding clinical progression of cases is a key public health priority that informs optimal resource allocation during an emergency. Using data from Shenzhen, China, where all cases were monitored in hospital and symptom profiles and clinical and lab results were available starting from early stages of clinical course, we characterized clinical progression of COVID-19 cases and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources. Epidemiological, demographic, laboratory, clinical, and outcome data were extracted from electronic medical records. We found that those who progressed to the severe stage, developed acute respiratory distress syndrome, and were admitted to the intensive care unit (ICU) progressed on average 9.5 days (95%CI 8.7,10.3), 11.0 days (95%CI 9.7,12.3), and 10.5 days (95%CI 8.2,13.3) after symptom onset, respectively. We estimated that patients who were admitted to ICUs remained there for an average of 34.4 days (95%CI 24.1,43.2) and the average time on a ventilator was 28.5 days (95%CI 20.0,39.1) among those requiring mechanical ventilation. The median length of hospital stay was 21.3 days (95%CI, 20.5, 22.2) for the mild or moderate cases who did not progress to the severe stage, but increased to 52.1 days (95%CI, 43.3, 59.5) for those who required ICU admission. Clear characterization of clinical progression informs planning for healthcare resource allocation during COVID-19 outbreaks and provides a basis that helps assess the effectiveness of new treatment and therapeutics.

negative: Estimation of the Probability of Reinfection With COVID-19 by the Susceptible-Exposed-Infectious-Removed-Undetectable-Susceptible Model BACKGROUND: With the sensitivity of the polymerase chain reaction test used to detect the presence of the virus in the human host, the worldwide health community has been able to record a large number of the recovered population. OBJECTIVE: The aim of this study was to evaluate the probability of reinfection in the recovered class and the model equations, which exhibits the disease-free equilibrium state for the coronavirus disease. METHODS: The model differential equation was evaluated for the disease-free equilibrium for the case of reinfection as well as the existence and stability criteria for the disease, using the model proportions. This evaluation shows that the criteria for a local or worldwide asymptotic stability with a basic reproductive number (R(0)=0) were satisfied. Hence, there is a chance of no secondary reinfections from the recovered population, as the rate of incidence of the recovered population vanishes (ie, B=0). RESULTS: With a total of about 900,000 infected cases worldwide, numerical simulations for this study were carried out to complement the analytical results and investigate the effect that the implementation of quarantine and observation procedures has on the projection of further virus spread. CONCLUSIONS: As shown by the results, the proportion of the infected population, in the absence of a curative vaccination, will continue to grow worldwide; meanwhile, the recovery rate will continue slowly, which means that the ratio of infection rate to recovery rate will determine the death rate that is recorded. Most significant for this study is the rate of reinfection by the recovered population, which will decline to zero over time as the virus is cleared clinically from the system of the recovered class.

negative: Expert consensus on the prevention and treatment of substance use and addictive behaviour-related disorders during the COVID-19 pandemic

negative: Epidemiological Characteristics of COVID-19: A Systemic Review and Meta-Analysis Background: Our understanding of the corona virus disease 2019 (COVID-19) continues to evolve. However, there are many unknowns about its epidemiology. Purpose: To synthesize the number of deaths from confirmed COVID-19 cases, incubation period, as well as time from onset of COVID-19 symptoms to first medical visit, ICU admission, recovery and death of COVID-19. Data Sources: MEDLINE, Embase, and Google Scholar from December 01, 2019 through to March 11, 2020 without language restrictions as well as bibliographies of relevant articles. Study Selection: Quantitative studies that recruited people living with or died due to COVID-19. Data Extraction: Two independent reviewers extracted the data. Conflicts were resolved through discussion with a senior author. Data Synthesis: Out of 1675 non-duplicate studies identified, 57 were included. Pooled mean incubation period was 5.84 (99% CI: 4.83, 6.85) days. Pooled mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.82 (95% CI: 3.48, 6.15), ICU admission was 10.48 (95% CI: 9.80, 11.16), recovery was 17.76 (95% CI: 12.64, 22.87), and until death was 15.93 (95% CI: 13.07, 18.79). Pooled probability of COVID-19-related death was 0.02 (95% CI: 0.02, 0.03). Limitations: Studies are observational and findings are mainly based on studies that recruited patient from clinics and hospitals and so may be biased toward more severe cases. Conclusion: We found that the incubation period and lag between the onset of symptoms and diagnosis of COVID-19 is longer than other respiratory viral infections including MERS and SARS; however, the current policy of 14 days of mandatory quarantine for everyone might be too conservative. Longer quarantine periods might be more justified for extreme cases.

negative: Effects of air pollutants on the transmission and severity of respiratory viral infections Particulate matter, sulfur dioxide, nitrogen oxides, ozone, carbon monoxide, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) are among the outdoor air pollutants that are major factors in diseases, causing especially adverse respiratory effects in humans. On the other hand, the role of respiratory viruses in the pathogenesis of severe respiratory infections is an issue of great importance. The present literature review was aimed at assessing the potential effects of air pollutants on the transmission and severity of respiratory viral infections. We have reviewed the scientific literature regarding the association of outdoor air pollution and respiratory viruses on respiratory diseases. Evidence supports a clear association between air concentrations of some pollutants and human respiratory viruses interacting to adversely affect the respiratory system. Given the undoubted importance and topicality of the subject, we have paid special attention to the association between air pollutants and the transmission and severity of the effects caused by the coronavirus named SARS-CoV-2, which causes the COVID-19. Although to date, and by obvious reasons, the number of studies on this issue are still scarce, most results indicate that chronic exposure to air pollutants delays/complicates recovery of patients of COVID-19 and leads to more severe and lethal forms of this disease. This deserves immediate and in-depth experimental investigations.

negative: Mathematical modeling of COVID-19 transmission and mitigation strategies in the population of Ontario, Canada Background: We evaluated how non-pharmaceutical interventions could be used to control the COVID-19 pandemic and reduce the burden on the healthcare system Methods: Using an age-structured compartmental model of COVID-19 transmission in the population of Ontario, Canada, we compared a base case with limited testing, isolation, and quarantine to scenarios with: enhanced case finding;restrictive social distancing measures;or a combination of enhanced case finding and less restrictive social distancing Interventions were either implemented for fixed durations or dynamically cycled on and off, based on projected ICU bed occupancy We present median and credible intervals (CrI) from 100 replicates per scenario using a two-year time horizon Results: We estimated that 56% (95% CrI: 42-63%) of the Ontario population would be infected over the course of the epidemic in the base case At the epidemic peak, we projected 107,000 (95% CrI: 60,760-149,000) cases in hospital and 55,500 (95% CrI: 32,700-75,200) cases in ICU For fixed duration scenarios, all interventions were projected to delay and reduce the height of the epidemic peak relative to the base case, with restrictive social distancing estimated to have the greatest effect Longer duration interventions were more effective Dynamic interventions were projected to reduce the proportion of the population infected at the end of the two-year period Dynamic social distancing interventions could reduce the median number of cases in ICU below current estimates of Ontario's ICU capacity Interpretation: Without significant social distancing or a combination of moderate social distancing with enhanced case finding, we project that ICU resources would be overwhelmed Dynamic social distancing could maintain health system capacity and also allow periodic psychological and economic respite for populations ### Competing Interest Statement The authors have declared no competing interest ### Funding Statement The research was supported by a grant to DNF from the Canadians Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360) ### Author Declarations All relevant ethical guidelines have been followed;any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials gov I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance) Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable Yes Data are available from the corresponding author on request

negative: COVID-19 pandemic: examining the faces of spatial differences in the morbidity and mortality in sub-Saharan Africa, Europe and USA. Background: COVID-19, the disease associated with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently a global pandemic with several thousands of confirmed cases of infection and death. However, the death rate across affected countries shows variation deserving of critical evaluation. Methods: In this study, we evaluated differentials in COVID-19 confirmed cases of infection and associated deaths of selected countries in Sub-Sahara Africa (Nigeria and Ghana), South Africa, Europe (Italy, Spain, Sweden and UK) and USA. Data acquired for various standard databases on mutational shift of the SARS-CoV-2 virus based on geographical location, BCG vaccination policy, malaria endemicity, climatic conditions (temperature), differential healthcare approaches were evaluated over a period of 45 days from the date of reporting the index case. Results: The number of confirmed cases of infection and associated deaths in Sub-Sahara Africa were found to be very low compared to the very high values in Europe and USA over the same period. Recovery rate from COVID-19 is not correlated with the mutational attributes of the virus with the sequenced strain from Nigeria having no significant difference (p>0.05) from other geographical regions. Significantly higher (p<0.05) infection rate and mortality from COVID-19 were observed in countries (Europe and USA) without a current universal BCG vaccination policy compared to those with one (Sub-Sahara African countries). Countries with high malaria burden had significantly lower (p<0.05) cases of COVID-19 than those with low malaria burden. A strong negative correlation (-0.595) between mean annual temperature and COVID-19 infection and death was observed with 14.8% variances between temperature and COVID-19 occurrence among the countries. A clear distinction was observed in the COVID-19 disease management between the developed countries (Europe and USA) and Sub-Sahara Africa. Conclusions: The study established that the wide variation in the outcome of the COVID-19 disease burden in the selected countries are attributable largely to climatic condition (temperature) and differential healthcare approaches to management of the disease. We recommend consideration and mainstreaming of these findings for urgent intervention and management of COVID-19 across these continents.

negative: Risk factors for chronic post-traumatic stress disorder (PTSD) in SARS survivors Abstract Background Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric diagnoses among survivors of severe acute respiratory syndrome (SARS). Objectives The objective of this study was to identify the predictors of chronic PTSD in SARS survivors. Design PTSD at 30 months after the SARS outbreak was assessed by the Structured Clinical Interview for the DSM-IV. Survivors' demographic data, medical information and psychosocial variables were collected for risk factor analysis. Results Multivariate logistic regression analysis showed that female gender as well as the presence of chronic medical illnesses diagnosed before the onset of SARS and avascular necrosis were independent predictors of PTSD at 30 months post-SARS. Associated factors included higher-chance external locus of control, higher functional disability and higher average pain intensity. Conclusion The study of PTSD at 30 months post-SARS showed that the predictive value of acute medical variables may fade out. Our findings do not support some prior hypotheses that the use of high dose corticosteroids is protective against the development of PTSD. On the contrary, the adversity both before and after the SARS outbreak may be more important in hindering recovery from PTSD. The risk factor analysis can not only improve the detection of hidden psychiatric complications but also provide insight for the possible model of care delivery for the SARS survivors. With the complex interaction of the biopsychosocial challenges of SARS, an integrated multidisciplinary clinic setting may be a superior approach in the long-term management of complicated PTSD cases.

negative: SARS-CoV-2 and gastrointestinal tract: the dark side of the pandemic

negative: Recovery from COVID‐19 in two patients with coexisted HIV infection COVID‐19 has become a global health concern. HIV‐infected patients are particularly vulnerable to COVID‐19 due to their immune‐compromised status. The clinical manifestations and clinical outcomes of these patients are not clear. In this report, we presented two special COVID‐19 patients with HIV infection and other comorbidities. We described the clinical characteristics, clinical manifestations, treatments and clinical outcomes of both patients. One patient with prior HIV‐infection continued anti‐HIV treatment when diagnosed with COVID‐19. The other patient was newly diagnosed with HIV‐infection when diagnosed with COVID‐19 and had not begun anti‐HIV treatment. Both patients were treated with anti‐viral, antibiotics, oxygen treatment and supportive care and recovered from severe pneumonia. The experience of these two cases suggested that COVID‐19 patients with HIV infection could still have satisfactory clinical outcomes following proper medical care. This article is protected by copyright. All rights reserved.

negative: Are there gender-specific aspects of gastric banding? Data analysis from the quality assurance study of the surgical treatment of obesity in Germany. BACKGROUND Since 1 January 2005, the situation of bariatric surgery has been examined in Germany. All data are registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg. METHODS Data collection on the results of gastric banding procedures was started in 2005, and the data are registered in an online database. Follow-up data were collected once a year. Participation in the quality assurance study is voluntary. RESULTS Since 2005, 3,453 gastric banding procedures have been performed at 88 hospitals. The mean age of patients was 40.7 years, and the mean body mass index (BMI) was 45.2 kg/m2. BMI and comorbidities are significantly higher in male patients. Regarding gender-specific aspects, there are no significant differences in the perioperative complication rates. The amelioration rate of comorbidities in male patients is lower than in female patients. CONCLUSION Gastric banding in Germany is generally performed in patients with a BMI below 45 kg/m2. The perioperative complication rate is low. Data from the nationwide survey of the German Bariatric Surgery Registry show significant differences in preoperative comorbidities and their amelioration between male and female patients. There is a need for further evaluation of gender-specific aspects of gastric banding procedures to optimize patient selection, reduce specific postoperative complications, and achieve long-term effects on weight loss and remission of comorbidities.

negative: The Powerful Immune System Against Powerful COVID-19: A Hypothesis Abstract On March 11, 2020, the World Health Organization declared the coronavirus outbreak a pandemic. Since December 2019, the world has experienced an outbreak of coronavirus disease 2019 (COVID-19). Epidemiology, risk factors, and clinical characteristics of patients with COVID-19 have been reported but the factors affecting the immune system against COVID-19 have not been well described. In this article, we provide a novel hypothesis to describe how an increase in cellular adenosine triphosphate (c-ATP) can potentially improve the efficiency of innate and adaptive immune systems to either prevent and fight off COVID-19.

negative: Report of a series of healthy term newborns from convalescent mothers with COVID-19. BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable virus associated with a significantly increased risk of complications among the infected population. Few data are available for the outcome of pregnancy complicated by serious respiratory disease due to SARS-CoV-2 infection. AIM We herein report a series of four neonates whose mothers had recovered from new coronavirus 2019 disease (COVID-19) diagnosed in the third trimester of pregnancy. METHODS pregnant women with documented COVID-19 infection during their pregnancy, who gave birth in Parma Hospital, University of Parma, Italy, in March and April 2020, during the peak of incidence of COVID-19 in Italy. Clinical records and laboratory tests were retrospectively reviewed. RESULTS All neonates were delivered at term in good conditions without congenital COVID-19 infection. CONCLUSIONS Findings from our series of cases indicated that adverse effects on foetuses from pregnancies complicated by COVID-19 infection in late pregnancy are unlikely.

negative: Rapid Scholarly Dissemination and Cardiovascular Community Engagement to Combat the Infodemic of the COVID-19 Pandemic

negative: Efficacy and Safety of Lianhuaqingwen Capsules, a repurposed Chinese Herb, in Patients with Coronavirus disease 2019: A multicenter, prospective, randomized controlled trial BACKGROUND: Coronavirus disease 2019 (Covid-19) has resulted in a global outbreak. Few existing targeted medications are available. Lianhuaqingwen (LH) capsule, a repurposed marketed Chinese herb product, has been proven effective for influenza. PURPOSE: To determine the safety and efficacy of LH capsule in patients with Covid-19. METHODS: We did a prospective multicenter open-label randomized controlled trial on LH capsule in confirmed cases with Covid-19. Patients were randomized to receive usual treatment alone or in combination with LH capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the rate of symptom (fever, fatigue, coughing) recovery. RESULTS: We included 284 patients (142 each in treatment and control group) in the full-analysis set. The recovery rate was significantly higher in treatment group as compared with control group (91.5% vs. 82.4%, P=0.022). The median time to symptom recovery was markedly shorter in treatment group (median: 7 vs. 10 days, P<0.001). Time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) was also significantly shorter in treatment group (all P<0.001). The rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, P<0.001) and clinical cure (78.9% vs. 66.2%, P=0.017) was also higher in treatment group. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings (both P>0.05). No serious adverse events were reported. CONCLUSION: In light of the safety and effectiveness profiles, LH capsules could be considered to ameliorate clinical symptoms of Covid-19.

negative: Clinical course and mortality risk of severe COVID-19

negative: Forecasting the Impact of Coronavirus Disease During Delivery Hospitalization: An Aid for Resources Utilization Abstract Background The ongoing Coronavirus disease (COVID-19) pandemic has severely impacted the United States. In cases of infectious disease outbreak, forecasting models are often developed for resources utilization. Pregnancy and delivery pose unique challenges, given the altered maternal immune system and the fact that the majority of American women choose to deliver in the hospital setting. Objectives The aim of our study is to forecast the incidence of COVID-19 in general population and to forecast the overall incidence, severe cases, critical cases and fatal COVID-19 cases during delivery hospitalization in the United States. Study design We use a phenomenological model with generalized logistic growth models to forecast the incidence of COVID-19 in the United States from 4/15/2020 – 12/31/2020. Incidence data from 3/1/2020 – 4/14/2020 were used to provide best-fit model solution. Subsequently, Monte-Carlo simulation was performed for each week from 3/1/2020 – 12/31/2020 to estimate the incidence of COVID-19 in delivery hospitalizations using the available data estimate. Results From 3/1/2020 – 12/31/2020, our model forecasted a total of 860,475 cases of COVID-19 in general population across the United States. The cumulative incidence for COVID-19 during delivery hospitalization is anticipated to be 16,601 (95% CI, 9,711 – 23,491) cases. Among those, 3,308 (95% CI, 1,755 – 4,861) cases are expected to be severe, 681 (95% CI, 1324 – 1,038) critical and 52 (95% CI, 23 – 81) maternal mortality. Assuming similar baseline maternal mortality rate as the year of 2018, we projected an increase in maternal mortality rate in the US to at least 18.7 (95% CI, 18.0 – 19.5) deaths per 100,000 live birth as a direct result of COVID-19. Conclusions COVID-19 infection in pregnant women is expected to severely impact obstetrical care. From 3/1/2020 – 12/31/2020, we project 3,308 severe and 681 critical cases, with about 52 COVID-19 related maternal mortalities during delivery hospitalization in the United States. These data might be helpful for counseling and resource allocation.

negative: Data analytics for novel coronavirus disease This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19.

negative: Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19): quels risques pour leur santé mentale? RÉSUMÉ Objectifs: La pandémie de la maladie à coronavirus (COVID-19) a provoqué une crise sanitaire majeure et mis en quarantaine la moitié de la population planétaire. En France, elle a provoqué une réorganisation en urgence de l’offre de soins mobilisant les soignants dans un climat d’incertitude. L'objectif du présent article est de faire le point sur les risques associés à l’exposition des soignants au COVID-19 pour leur santé mentale. Méthodes: Les auteurs ont conduit une revue de la littérature internationale tenant compte des données des précédentes épidémies (SARS-CoV-1, H1N1) et des données plus récentes concernant le COVID-19. Résultats: Les caractéristiques de cette pandémie (rapidité de diffusion, connaissances incertaines, sévérité, morts de soignants) ont installé un climat anxiogène. Des facteurs organisationnels peuvent être source de stress : déficit d’équipement de protection individuel, réaffectation de postes, manque de communication, manque de matériels de soins, bouleversement de la vie quotidienne familiale et sociale. D’autres facteurs de risque sont identifiés comme l’absence de soutien, la crainte de contaminer un proche, l’isolement ou la stigmatisation sociale, le haut niveau de stress au travail, ou les patterns d’attachement insécure. Les soignants ont ainsi un risque augmenté d’anxiété, de dépression, d’épuisement, d’addiction et de trouble de stress post-traumatique. Conclusions: Cette crise sanitaire devrait nous aider à mieux comprendre la vulnérabilité des soignants à la souffrance psychologique afin de renforcer les stratégies de prévention primaire et la formation aux enjeux psychologiques des soins, de la relation, et de la gestion des situations de crises sanitaires. ABSTRACT Objectives: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide an up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. Methods: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. Results: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concern about not being able to provide competent care if deployed to new area, concern about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. Conclusions: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

negative: Coronavirus Disease 19 (COVID-19) during chemoradiation for locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC)

negative: The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.

negative: Evaluation of the Broad-Range PCR-Electrospray Ionization Mass Spectrometry (PCR/ESI-MS) System and Virus Microarrays for Virus Detection Advanced nucleic acid-based technologies are powerful research tools for novel virus discovery but need to be standardized for broader applications such as virus detection in biological products and clinical samples. We have used well-characterized retrovirus stocks to evaluate the limit of detection (LOD) for broad-range PCR with electrospray ionization mass spectrometry (PCR/ESI-MS or PLEX-ID), RT-PCR assays, and virus microarrays. The results indicated that in the absence of background cellular nucleic acids, PLEX-ID and RT-PCR had a similar LOD for xenotropic murine retrovirus-related virus (XMRV; 3.12 particles per µL) whereas sensitivity of virus detection was 10-fold greater using virus microarrays. When virus was spiked into a background of cellular nucleic acids, the LOD using PLEX-ID remained the same, whereas virus detection by RT-PCR was 10-fold less sensitive, and no virus could be detected by microarrays. Expected endogenous retrovirus (ERV) sequences were detected in cell lines tested and known species-specific viral sequences were detected in bovine serum and porcine trypsin. A follow-up strategy was developed using PCR amplification, nucleotide sequencing, and bioinformatics to demonstrate that an RD114-like retrovirus sequence that was detected by PLEX-ID in canine cell lines (Madin-Darby canine kidney (MDCK) and Cf2Th canine thymus) was due to defective, endogenous gammaretrovirus-related sequences.

negative: Initial events in bovine coronavirus infection: analysis through immunogold probes and lysosomotropic inhibitors The early events in the infection of human rectal tumor cells by bovine coronavirus were investigated by colloidal gold-mediated immunoelectron microscopy and by analysis of the effect of lysosomotropic weak bases on virus yield. Electron microscopic studies revealed sites of fusion between the virus envelope and the plasmalemma but fusion events along intracellular membranes were not observed despite extensive searches. Virion-antibody-colloidal gold complexes were, in fact, endocytosed by synchronously infected cells. These complexes were apparently non-infectious, and they accumulated in vacuoles that resembled secondary lysosomes. Exposure of cells to ammonium chloride or to methylamine during the first hour of infection had little inhibitory effect on the production of infectious virus. Chloroquine treatments were inhibitory but this effect depended on relatively late events in the infectious process. The chloroquine inhibitory step blocked infection of virus adsorbed to cells that were exposed to buffers in the pH range of 4.4 to 8.4. These findings indicate that BCV penetrates its host cell by direct fusion with the plasmalemma and does not require an acidic intracellular compartment for infectious entry.

negative: Spreading Analysis of COVID-19 Epidemic in Bangladesh by Dynamical Mathematical Modelling The coronavirus disease 2019 (COVID-19), which emerged from Wuhan, China, is now a pandemic, affecting across the globe. Bangladesh also is experiencing the rapid growth of COVID-19 infection and death cases started from 8th March 2020. The purpose of providing a simple yet effective explanatory model for prediction of the future evolution of the contagion and verification of the effectiveness of the containment and lockdown measures in Bangladesh. In this study, using a modified SIR (Susceptible-Infected-Recovered) model a forecast is generated to predict the trends of COVID-19 cases in Bangladesh. The epidemic model was proposed to accommodate the effects of lockdown and individual based precautionary measures. Data has been taken and analyzed for before and after the movement control order (MCO) and during the MCO period. Modified SIR model in this work offers us an idea how the outbreak would progress based on the current data. It also has estimated that, the peak in terms of the number of infected cases will start from last of June 2020. For the total population (100%) the model gets the peaks at 214875 (infected cases) and 7743 (death cases). For the 90% population, the model shows the peaks at 244356 (infected cases) and 9100 (death cases). Analysis revealed that the lockdown and recommended individual hygiene can slow down the outbreak but unable to eradicate the disease from the society. With the current infection and death rate and existing level of personal precautionary the number of infected individuals will be increasing.

negative: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.

negative: Virus-induced acute respiratory distress syndrome: Epidemiology, management and outcome Summary The acute respiratory distress syndrome (ARDS) can be induced by viral diseases, with two virus types being responsible: respiratory viruses that cause community-acquired viral pneumonia and Herpesviridae that cause nosocomial viral pneumonia. Among the respiratory viruses that can affect the lung and cause ARDS, pandemic viruses head the list, with influenza viruses H5N1 and H1N1 2009 being the most recently identified. However, other viruses can cause severe ARDS. Notably, a novel coronavirus was responsible for the severe acute respiratory syndrome outbreak in 2003. Apart from these pandemic viruses, respiratory viruses are rarely responsible for viral pneumonia and ARDS. Other than antiviral drug (mainly oseltamivir) administration and avoidance of corticosteroids, management of ARDS due to these viruses does not differ from that for ARDS caused by other diseases. Among Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) are the two viruses causing nosocomial viral pneumonia that can evolve into ARDS. HSV is frequently recovered in the respiratory tract of mechanically ventilated patients and can sometimes be responsible for HSV bronchopneumonitis. Although not evaluated for this indication, acyclovir can be a therapeutic option for patients with HSV bronchopneumonitis and ARDS. CMV pneumonia can also occur in mechanically ventilated patients, but is difficult to diagnose because virus recovery does not necessarily mean viral disease. Ganciclovir can be considered for patients with ARDS and histology- or cytology-proven CMV pneumonia.

negative: Discrete SIRIR modelling using empirical infection data shows that SARS-CoV-2 infection provides short-term immunity The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, is now a global pandemic. Since December 2019, it has infected millions of people, caused the deaths of hundreds of thousands, and resulted in incalculable social and economic damage. Understanding the infectivity and transmission dynamics of the virus is essential for understanding how best to reduce mortality whilst ensuring minimal social restrictions to the lives of the general population. Anecdotal evidence is available, but detailed studies have not yet revealed whether infection with the virus results in immunity. In this work, we have extended the generic SIR framework to analyse empirical infection and fatality data from different regions to investigate the reinfection frequency of the disease. Our model predicts that cases of reinfection should have been observed by now if primary SARS-CoV-2 infection did not protect from subsequent exposure in the short term, however, no such cases have been documented. This work, therefore, provides a useful insight for serological testing strategies, lockdown easing and vaccine design.

negative: Why estimating population-based case fatality rates during epidemics may be misleading Different ways of calculating mortality ratios during epidemics can yield widely different results, particularly during the COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the length of time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of infected cases to date. Using available data on the recent SARS-CoV-2 outbreaks and simple assumptions, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose a more systematic method to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and errors in the data.

negative: Postmortem Lung Findings in an Asthmatic with Coronavirus Disease 2019 (COVID-19) Abstract Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in coronavirus disease 2019 (COVID-19) patients, particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old asthmatic man, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than two weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage (DAD) and a fibrinous pneumonia. The presence of DAD is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS), and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza. The relative contribution of mucus plugging to his hypoxemia is unknown.

negative: Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Zâ=â9.738, Pâ<â0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χâ=â22.105, Pâ<â0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Zâ=â3.216, Pâ=â0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χâ=â60.905, Pâ<â0.001) and expectoration (32.1% vs. 12.1%, χâ=â13.250, Pâ<â0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Zâ=â10.625, Pâ<â0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10/L, Zâ=â7.618, Pâ<â0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10/L, Zâ=â8.037, Pâ<â0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Zâ=â10.315, Pâ<â0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Zâ=â5.242, Pâ<â0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Zâ=â2.592, Pâ=â0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Zâ=â7.308, Pâ<â0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] µmol/L, Zâ=â6.478, Pâ<â0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Zâ=â10.206, Pâ<â0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Zâ=â1.219, Pâ=â0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χâ=â148.105, Pâ<â0.001), acute cardiac injury (59.6% vs. 0.9%, χâ=â93.222, Pâ<â0.001), acute kidney injury (18.3% vs. 0%, χâ=â23.257, Pâ<â0.001), shock (11.9% vs. 0%, χâ=â14.618, Pâ<â0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χâ=â7.655, Pâ=â0.006). CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.

negative: Studying Vulnerable Populations in the Context of Enhanced Vulnerability The many needs that arise during and immediately following a disaster normally stretch local and national governments and humanitarian organisations to the limit. Both human and financial resources are often inadequate to meet the requirements of medical care, clean water, sufficient food and shelter for victims of the disaster. How, then, can one justify conducting research during or shortly after disaster strikes? People caught in the wake of a disaster are rendered vulnerable by a variety of factors, including injuries, fear, grief, inadequate food and water, loss of housing, and disease outbreaks that sometimes accompany disasters. In addition, an entire population or segments of the population may have been vulnerable to some extent before the disaster struck: they may have food insecurity, lack of potable water, inadequate health care, or be at risk from endemic diseases. Therefore, many people are rendered doubly or even triply vulnerable in the wake of a disaster. The ethical question that arises is whether the vulnerability of victims of a disaster militates against conducting research during or soon after the event.

negative: Identification of canine coronavirus strains from feces by S gene nested PCR and molecular characterization of a new Australian isolate. A nested PCR (nPCR) assay for the detection of canine coronavirus (CCV) in fecal samples is described. The target sequence for the assay was a 514-bp fragment within the spike (S) glycoprotein gene. The sensitivity of the assay is extremely high, detecting as little as 25 50% tissue culture infective doses per g of unprocessed feces. A clinical trial using dogs challenged orally with CCV SA4 and CCV NVSL was used to compare viral isolation and the nPCR assay as detection techniques over a 2-week period of infection. Virus isolation detected CCV shedding from day 4 to 9 postchallenge, while the nPCR assay detected CCV shedding from day 4 to 13 postchallenge. Cloning and sequencing of the nPCR assay product enabled investigation of the evolutionary relationships between strains within the S gene. The simple and rapid procedure described here makes this assay an ideal alternative technique to electron microscopy and viral isolation in cell culture for detection of CCV shedding in feces. The described assay also provides a method of identifying new strains of CCV without the complicated and time-consuming practice of raising antibodies to individual strains. This is illustrated by the identification, for the first time, of an Australian isolate of CCV (UWSMN-1).

negative: Do Weather Temperature and Median-age affect COVID-19 Transmission? It was observed that the coldest countries and the eldest in terms of median-age were most distressed by COVID-19 pandemic, while the warmest countries and that have younger-aged population were the least affected. Therefore, this study utilized the non-linear least squares method to estimate the impact of weather temperatures and median age on COVID-19 cases per million in thirty-nine countries divided into two groups. The first group composed of twenty-four countries that announced the first COVID-19 case in January 2020, while the second group contains fifteen countries that witnessed the pandemic for the first time in February of the same year. The study revealed some major findings, which are: COVID-19 cases per million were not significantly affected by weather temperature or the median age in “January-group” countries (after 72.67 days on average), while COVID-19 cases per million increased significantly by decreasing temperatures, and increasing the median age in case of “February-group” countries (after an average of 44.80 days). This means that weather temperature and median age may influence the transmission rates of COVID-19 in its early stages, while weather temperature or median age no longer have effects in the advanced stages of the pandemic.

negative: Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease BACKGROUND: The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent. METHODS: We used homozygous (+/+) and heterozygous (+/−) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD(50)) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection. RESULTS: hDPP4(+/+) mice were unexpectedly more resistant than hDPP4(+/−) mice to MERS-CoV infection, as judged by increased LD(50), reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology. CONCLUSIONS: Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis.

negative: The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future Abstract At the end of December 2019, a novel coronavirus, 2019-nCoV, caused an outbreak of pneumonia spreading from Wuhan, Hubei province, to the whole country of China, which has posed great threats to public health and attracted enormous attention around the world. To date, there are no clinically approved vaccines or antiviral drugs available for these human coronavirus infections. Intensive research on the novel emerging human infectious coronaviruses is urgently needed to elucidate their route of transmission and pathogenic mechanisms, and to identify potential drug targets, which would promote the development of effective preventive and therapeutic countermeasures. Herein, we describe the epidemic and etiological characteristics of 2019-nCoV, discuss its essential biological features, including tropism and receptor usage, summarize approaches for disease prevention and treatment, and speculate on the transmission route of 2019-nCoV.

negative: Case Report: Death due to COVID-19 in Three Brothers We report fatal cases of novel coronavirus disease (COVID-19) in three brothers in Iran. An increased susceptibility to specific pathogens has been reported for a number of genetic defects. Considering the fact that most of them who are affected by COVID-19 recover, deaths in three brothers who lived separately and had no known underlying disease suggest genetic predisposition to COVID-19 in some individuals.

negative: Use Stones from Another Mountain to Polish One’s Jade: Learn from MERS Studies toexplore potential mechanisms underlying the effect of diabetes mellitus on COVID-19/ 中华内分泌代谢杂志 Epidemiology studies suggest that comorbid diabetes may have negative impact on the progression and severity of the coronavirus disease 2019 (COVID-19), which first occurred in Wuhan. However, the exact mechanism remains unclear. A recent study on another type of coronavirus infection, Middle East Respiratory Syndrome (MERS), investigated its relationship with diabetes. This essay aims to give a brief introduction to this report and related studies, and to propose suggestions on what we can learn from these investigations to conduct further studies on the potential mechanisms underlying the effect of diabetes mellitus on COVID-19.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.

negative: Interferon and cytokine responses to SARS-coronavirus infection Abstract The sudden emergence of severe acute respiratory syndrome (SARS) has boosted research on innate immune responses to coronaviruses. It is now well established that the causative agent, a newly identified coronavirus termed SARS-CoV, employs multiple passive and active mechanisms to avoid induction of the antiviral type I interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are strongly upregulated. The imbalance in the IFN response is thought to contribute to the establishment of viremia early in infection, whereas the production of chemokines by infected organs may be responsible for (i) massive immune cell infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of adaptive immunity. Here, we will review the most recent findings on the interaction of SARS-CoV and related Coronaviridae members with the type I interferon and cytokine responses and discuss implications for pathogenesis and therapy.

negative: Influence of socio-ecological factors on COVID-19 risk: a cross-sectional study based on 178 countries/regions worldwide BACKGROUND: The initial outbreak of COVID-19 caused by SARS-CoV-2 in China in 2019 has been severely tested in other countries worldwide. We aimed to describe the spatial distribution of the COVID-19 pandemic worldwide and assess the effects of various socio-ecological factors on COVID-19 risk. METHODS: We collected COVID-19 pandemic infection data and social-ecological data of 178 countries/regions worldwide from three database. We used spatial econometrics method to assess the global and local correlation of COVID-19 risk indicators for COVID-19. To estimate the adjusted incidence rate ratio (IRR), we modelled negative binomial regression analysis with spatial information and socio-ecological factors. FINDINGS: The study indicated that 37, 29 and 39 countries/regions were strongly opposite from the IR, CMR and DCI index "spatial autocorrelation hypothesis", respectively. The IRs were significantly positively associated with GDP per capita, the use of at least basic sanitation services and social insurance program coverage, and were significantly negatively associated with the proportion of the population spending more than 25% of household consumption or income on out-of-pocket health care expenses and the poverty headcount ratio at the national poverty lines. The CMR was significantly positively associated with urban populations, GDP per capita and current health expenditure, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives, and poverty headcount ratio at the national poverty lines. The DCI was significantly positively associated with urban populations, population density and researchers in R&D, and was significantly negatively associated with the number of hospital beds, number of nurses and midwives and poverty headcount ratio at the national poverty lines. We also found that climatic factors were not significantly associated with COVID-19 risk. CONCLUSION: Countries/regions should pay more attention to controlling population flow, improving diagnosis and treatment capacity, and improving public welfare policies.

negative: Cardiological society of India position statement on COVID-19 and heart failure

negative: Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study BACKGROUND: Research evidence exists that poor prognosis is common in Middle East respiratory syndrome coronavirus (MERS‐CoV) patients. OBJECTIVES: This study estimates recovery delay intervals and identifies associated factors in a sample of Saudi Arabian patients admitted for suspected MERS‐CoV and diagnosed by rRT‐PCR assay. METHODS: A multicenter retrospective study was conducted on 829 patients admitted between September 2012 and June 2016 and diagnosed by rRT‐PCR procedures to have MERS‐CoV and non‐MERS‐CoV infection in which 396 achieved recovery. Detailed medical charts were reviewed for each patient who achieved recovery. Time intervals in days were calculated from presentation to the initial rRT‐PCR diagnosis (diagnosis delay) and from the initial rRT‐PCR diagnosis to recovery (recovery delay). RESULTS: The median recovery delay in our sample was 5 days. According to the multivariate negative binomial model, elderly (age ≥ 65), MERS‐CoV infection, ICU admission, and abnormal radiology findings were associated with longer recovery delay (adjusted relative risk (aRR): 1.741, 2.138, 2.048, and 1.473, respectively). Camel contact and the presence of respiratory symptoms at presentation were associated with a shorter recovery delay (expedited recovery) (aRR: 0.267 and 0.537, respectively). Diagnosis delay is a positive predictor for recovery delay (r = .421; P = .001). CONCLUSIONS: The study evidence supports that longer recovery delay was seen in patients of older age, MERS‐CoV infection, ICU admission, and abnormal radiology findings. Shorter recovery delay was found in patients who had camel contact and respiratory symptoms at presentation. These findings may help us understand clinical decision making on directing hospital resources toward prompt screening, monitoring, and implementing clinical recovery and treatment strategies.

negative: Covid-19: adverse mental health outcomes for healthcare workers

negative: Rehabilitation Response in Pandemics The WHO declared a pandemic due to the serious health risk posed by Coronavirus disease (COVID-19). The number of infected cases is on the rise globally with escalating human, economic and societal costs. COVID-19 survivors may suffer a range of clinical, functional and psychological impairments, resulting in disabilities. Many are amenable to rehabilitation intervention. The current focus of COVID-19 management is on public health measures and acute management. As patients transfer to sub-acute care or discharged to the community, rehabilitation services need to have a number of organizational and operational models in place to provide safe effective care for patients and health professionals. There is need for global action by professional organizations in developing a structured rehabilitation approach for international response to disasters, including pandemics. This report proposes development of a ‘Rehabilitation Response Plan’ to enable the International Society of Physical and Rehabilitation Medicine, to provide crucial leadership and governance role in liaison and coordination with the WHO (and other stakeholders), to provide rehabilitation input during current and future pandemics. The key considerations include following categories: Governance, Coordination, Communication, Evaluation, and Care-continuum. These will strengthen rehabilitation, assist in the effective delivery of services, provide advocacy, and an international coordinated perspective.

negative: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.

negative: Development and evaluation of a novel bioaerosol amplification unit (BAU) for improved viral aerosol collection Abstract A novel bioaerosol amplification unit (BAU) that increases the size of viral particles by condensational growth has been designed and evaluated for improved viral aerosol collection. In the BAU, water was used as the condensing vapor to preserve viability of virus, and supersaturation conditions for condensational growth of particles were achieved by either conductive cooling or mixing with hot, water-saturated air. MS2 bacteriophage (28nm) was used as the test agent, and changes in collection efficiency of an SKC Biosampler with and without the BAU were determined by assaying plaque-forming units (PFUs) in the collection medium. Results showed that the mixing-type BAU (mBAU) was a promising device for improved viral aerosol sampling. The number of viruses (PFU) collected in the Biosampler increased 2–3 fold after passing through the mBAU. However, PFU increases in the cooling-type BAU (cBAU) were insignificant. APS results likewise showed that the mBAU was better in growing particles than the cBAU. After growth, number concentrations of particles larger than 327nm in the cBAU and mBAU increased 1.3 and 15.0 fold, respectively. The relatively high molecular diffusivity of water vapor compared to the thermal diffusivity of air and the temperature gradient in the cBAU tube limited particle growth by causing condensation to occur predominantly at the colder wall.

negative: Risk of reactivation or reinfection of novel coronavirus (COVID-19)

negative: How Essential Is to Focus on Physician's Health and Burnout in Coronavirus (COVID-19) Pandemic? An infection of novel coronavirus (COVID-19) that originated from Wuhan city of China in December 2019 converted rapidly into pandemic by March 11, 2020. To date, the number of confirmed cases and deaths has risen exponentially in more than 200 countries, with an estimated crude mortality ratio of at least over 2%. The unpreparedness to tackle the unprecedented situation of coronavirus has contributed to the rising number of cases, which has generated an immense sense of fear and anxiety amongst the public. It has further resulted in the inadequacy and unavailability of essential medical supplies, physicians, and healthcare workers (HCW). Although the chief focus is on minimizing transmission through prevention, combating infection, and saving lives by ramping up the development of treatment and vaccines, very little attention is on the critical issue of physician burnout, resident burnout, and the psychological well-being of HCW. Until now, no significant steps have been taken by the authorities to minimize the COVID-19 specific contributing factors for burnout. The COVID-19 has posed strain on the entire healthcare system already, and it is vital to remediate the issue of physician and resident burnout urgently with concrete actions to avoid subsequent potential short-term and long-term adverse implications.

negative: COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

negative: Extra-respiratory manifestations of COVID-19 Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health threat. Although most patients with COVID-19 manifest fever and respiratory tract symptoms, SARS-CoV-2 infection may also involve other organs/systems and present with extra-respiratory manifestations, including cardiac, gastrointestinal, hepatic, renal, neurological, olfactory, gustatory, ocular, cutaneous and haematological symptoms. Occasionally, these extra-respiratory symptoms/signs represent the initial presentation of SARS-CoV-2 infection, prior to fever or respiratory manifestations. Therefore, this comprehensive review of the extra-respiratory manifestations of COVID-19 is intended to help clinicians better understand the range of clinical presentations associated with SARS-CoV-2 infection, allowing the consideration of COVID-19 in differential diagnoses. A screening test for SARS-CoV-2 should be performed when patients have these extra-respiratory manifestations. In addition, clinicians should be alerted to the adverse effects of anti-SARS-CoV-2 agents that can mimic the extra-respiratory manifestations of COVID-19. Moreover, some extra-respiratory manifestations, such as ocular and gastrointestinal involvement, may be caused by direct invasion of SARS-CoV-2. Therefore, protective measures should be taken while managing the associated clinical specimens. Finally, several extra-respiratory manifestations, such as cardiac involvement, acute kidney injury, coagulation disorders and thrombotic complications, could be associated with a poor prognosis.

negative: Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C–25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.

negative: Recovery of a neurovirulent human coronavirus OC43 from an infectious cDNA clone. This study describes the assembly of a full-length cDNA clone of human coronavirus (HCoV)-OC43 in a bacterial artificial chromosome (BAC). The BAC containing the full-length infectious cDNA (pBAC-OC43(FL)) was assembled using a two-part strategy. The first step consisted in the introduction of each end of the viral genome into the BAC with accessory sequences allowing proper transcription. The second step consisted in the insertion of the whole HCoV-OC43 cDNA genome into the BAC. To produce recombinant viral particles, pBAC-OC43(FL) was transfected into BHK-21 cells. Recombinant virus displayed the same phenotypic properties as the wild-type virus, including infectious virus titers produced in cell culture and neurovirulence in mice.

negative: The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals The global outbreak of coronavirus disease (COVID-19) has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, post-acute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with COVID-19. Clinicians across the nation’s rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands, and the strategies to meet the needs of this population. The complications from COVID-19 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting, and at home through ongoing therapy either in-person or via telehealth.

negative: Orthopedic Surgery Post COVID-19: An Opportunity for Innovation and Transformation

negative: Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3–7 days. Mainly initial symptoms were cough and low fever (37.3–38.0 °C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3–14, 6–8 and 7–9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.

negative: Mental health and emotional impact of COVID-19: Applying Health Belief Model for medical staff to general public of Pakistan

negative: Can post-exposure prophylaxis for COVID-19 be considered as an outbreak response strategy in long-term care hospitals? In the context of the ongoing global outbreak of coronavirus disease 2019 (COVID-19), management of exposure events is a concern. Long-term care hospitals (LTCHs) are particularly vulnerable to cluster outbreaks because facilities for patient isolation and healthcare personnel to care for these patients in isolation are difficult to arrange in a large outbreak situation. Although several drugs have been proposed as treatment options, there are no data on the effectiveness and safety of post-exposure prophylaxis (PEP) for COVID-19. After a large COVID-19 exposure event in an LTCH in Korea, PEP using hydroxychloroquine (HCQ) was administered to 211 individuals, including 189 patients and 22 careworkers, whose baseline polymerase chain reaction (PCR) tests for COVID-19 were negative. PEP was completed in 184 (97.4%) patients and 21 (95.5%) careworkers without serious adverse events. At the end of 14 days of quarantine, all follow-up PCR tests were negative. Based on our experience, further clinical studies are recommended for COVID-19 PEP.

negative: Six month radiological and physiological outcomes in severe acute respiratory syndrome (SARS) survivors. BACKGROUND The long term physiological and radiological outcomes of SARS survivors and their possible determinants are uncertain. METHODS SARS survivors in a follow up clinic in a regional hospital underwent high resolution computed tomography (HRCT) of the thorax and lung function tests 6 months after admission to hospital. The associations between the clinical and demographic data of the patients and the physiological and radiological outcomes were examined. RESULTS Fifty seven patients took part in the study. Lung function abnormalities were detected in 43 patients (75.4%), with restrictive defects (n = 16) being most common (28.1%). Radiological abnormalities of any degree were detected in 43 patients (75.4%). Only the use of pulse corticosteroids was associated with the presence of CT abnormalities (p = 0.043, OR 6.65, 95% CI 1.06 to 41.73). CONCLUSIONS Physiological and radiological abnormalities are still present in a considerable proportion of SARS survivors at 6 months.

negative: Geographical Variation in COVID-19 Cases, Prevalence, Recovery and Fatality Rate by Phase of National Lockdown in India, March 14-May 29, 2020 Background: Since the COVID-19 pandemic hit Indian states at varying speed, it is crucial to investigate the geographical pattern in COVID-19. We analyzed the geographical pattern of COVID-19 prevalence and mortality by the phase of national lockdown in India. Method: Using publicly available compiled data on COVID-19, we estimated the trends in new cases, period-prevalence rate (PPR), case recovery rate (CRR), and case fatality ratio (CFR) at national, state and district level. Findings: The age and sex are missing for more than 60 percent of the COVID-19 patients. There is an exponential increase in COVID-19 cases both at national and sub-national levels. The COVID-19 infected has jumped about 235 times ( from 567 cases in the pre-lockdown period to 1,33,669 in the fourth lockdown); the average daily new cases have increased from 57 in the first lockdown to 6,482 in the fourth lockdown; the average daily recovered persons from 4 to 3,819; the average daily death from 1 to 163. From first to the third lockdown, PPR (0.04 to 5.94), CRR (7.05 to 30.35) and CFR (1.76 to 1.89) have consistently escalated. At state-level, the maximum number of COVID-19 cases is found in the states of Maharashtra, Tamil Nadu, Delhi, and Gujarat contributing 66.75 percent of total cases. Whereas no cases found in some states, Kerela is the only state flattening the COVID-19 curve. The PPR is found to be highest in Delhi, followed by Maharastra. The highest recovery rate is observed in Kerala, till second lockdown; and in Andhra Pradesh in third lockdown. The highest case fatality ratio in the fourth lockdown is observed in Gujarat and Telangana. A few districts viz. like Mumbai (96.7); Chennai (63.66) and Ahmedabad (62.04) have the highest infection rate per 100 thousand population. Spatial analysis shows that clusters in Konkan coast especially in Maharashtra (Palghar, Mumbai, Thane and Pune); southern part from Tamil Nadu (Chennai, Chengalpattu and Thiruvallur), and the northern part of Jammu & Kashmir (Anantnag, Kulgam) are hot-spots for COVID-19 infection while central, northern and north-eastern regions of India are the cold-spots. Conclusion: India has been experiencing a rapid increase of COVID-19 cases since the second lockdown phase. There is huge geographical variation in COVID-19 pandemic with a concentration in some major cities and states while disaggregated data at local levels allows understanding the geographical disparity of the pandemic, the lack of age-sex information of the COVID-19 patients forbids to investigate the individual pattern of COVID-19 burden. Keyword: COVID-19; India; Case Fatality Rate; Case Recovery Rate; Period Prevalence Rate; Geographical variation

negative: COVID-19 Datasets: A Survey and Future Challenges In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.

negative: A Mini Review on Current Clinical and Research Findings for Children Suffering from COVID-19 Background: As the novel coronavirus triggering COVID-19 has broken out in Wuhan, China and spread rapidly worldwide, it threatens the lives of thousands of people and poses a global threat on the economies of the entire world. However, infection with COVID-19 is currently rare in children. Objective To discuss the latest findings and research focus on the basis of characteristics of children confirmed with COVID-19, and provide an insight into the future treatment and research direction. Methods: We searched the terms "COVID-19 OR coronavirus OR SARS-CoV-2" AND "Pediatric OR children" on PubMed, Embase, Cochrane library, NIH, CDC, and CNKI. The authors also reviewed the guidelines published on Chinese CDC and Chinese NHC. Results: We included 25 published literature references related to the epidemiology, clinical manifestation, accessary examination, treatment, and prognosis of pediatric patients with COVID-19. Conclusion: The numbers of children with COVID-19 pneumonia infection are small, and most of them come from family aggregation. Symptoms are mainly mild or even asymptomatic, which allow children to be a risk factor for transmission. Thus, strict epidemiological history screening is needed for early diagnosis and segregation. This holds especially for infants, who are more susceptible to infection than other age groups in pediatric age, but have most likely subtle and unspecific symptoms. They need to be paid more attention to. CT examination is a necessity for screening the suspected cases, because most of the pediatric patients are mild cases, and plain chest X-ray do not usually show the lesions or the detailed features. Therefore, early chest CT examination combined with pathogenic detection is a recommended clinical diagnosis scheme in children. The risk factors which may suggest severe or critical progress for children are: Fast respiratory rate and/or; lethargy and drowsiness mental state and/or; lactate progressively increasing and/or; imaging showed bilateral or multi lobed infiltration, pleural effusion or rapidly expending of lesions in a short period of time and/or; less than 3 months old or those who underly diseases. For those critical pediatric patients with positive SARS-CoV-2 diagnosis, polypnea may be the most common symptom. For treatment, the elevated PCT seen in children in contrast to adults suggests that the underlying coinfection/secondary infection may be more common in pediatric patients and appropriate antibacterial treatment should be considered. Once cytokine storm is found in these patients, anti-autoimmune or blood-purifying therapy should be given in time. Furthermore, effective isolation measures and appropriate psychological comfort need to be provided timely.

negative: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study Summary Background As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks. Methods In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time. Findings We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020. Interpretation News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions. Funding Fogarty International Center, US National Institutes of Health.

negative: SAA is a biomarker to distinguish the severity and prognosis of Coronavirus Disease 2019 (COVID-19) Abstract Background To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. Methods A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. Results COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. Conclusions SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.

negative: Clinical characteristics of 82 death cases with COVID-19 Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital′s electronic medical records according to previously designed standardized data collection forms. Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.

negative: Nosocomial Infection in the Intensive Care Unit

negative: Successful recovery from severe COVID‐19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab Although immunosuppressed patients may be more prone to SARS‐CoV‐2 infection with atypical presentation, long‐term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID‐19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID‐19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID‐19 of a kidney‐transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.

negative: Experimental and theoretical studies of solvent effects on the hydrogen bonds in homoconjugated cations of substituted 4-halo (Cl,Br) pyridine N-oxide derivatives Abstract Hydrogen bond OHO-type bridges formed between six substituted 4-halo (Cl,Br) pyridine N-oxide systems and their simple cations have been investigated by using the potentiometric titration method. The formation constants of these complexes (expressed as lg K BHB + ) have been determined in two non-aqueous aprotic solvents with different polarity, i.e., acetone (AC) and acetonitrile (AN). It has been observed that tri- and tetra-substituted pyridine N-oxides [B] and their cationic acids [BH+] form stable homocomplexed cations [BHB+] stabilized by O⋯H⋯O bridges in both solvents used. It has been found that the most stable homocomplexed system is formed by 3,5-dimethyl-4-chloropyridine N-oxide (3,5Me24ClPyO). The lg K BHB + values for this compound in acetone and acetonitrile are 3.15 and 2.82, respectively. Furthermore, by using ab initio methods at the RHF and MP2 levels utilizing the Gaussian 6-31++G∗∗ basis set, the energies of formation of the homocomplexed cations and Gibbs free energies have been determined in vacuo. The calculated energy parameters in vacuo have been compared with the cationic homoconjugation constants determined potentiometrically in acetone and acetonitrile to establish a correlation between these magnitudes. Additionally, the results of potentiometric measurements have been used to determine the acidity constants of the conjugate acids of N-oxides.

negative: The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals

negative: Ethnicity and COVID-19: an urgent public health research priority

negative: Mechanistic rationale of drugs, Primary endpoints, Geographical distribution of clinical trials against Severe acute respiratory syndrome-related coronavirus-2: A Systematic Review Objective To do a systematic review and critical appraisal of the ongoing clinical trials that are assessing various therapeutic interventions against SARS-CoV-2 with an aim to provide insight into the various interventions tested, clinical rationale, geographical distribution of the trials as well as the endpoints assessed in the studies. Design Rapid systematic review and critical appraisal of the ongoing clinical trials against SARS-CoV-2. Data sources ClinicalTrials.gov, World health organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Cochrane COVID registry were assessed till May 11th 2020. Study selection Studies on any intervention based randomized controlled trials (RCTs), prospective clinical studies on SARS-CoV-2 in patients [≥]18 years of age. Studies on autopsy series, preclinical studies, diagnostic methods, mathematical modelling, epidemiology and health services research, pediatric populations were excluded. Data extraction The data was extracted by two authors independently into pre-defined forms based on the SPIRIT 2013 checklist. The data was extracted on various domains such as trial number, study title, abstract of the study, interventions assessed, sample size, phase of the study, study sponsor, primary endpoint assessed and country of study. Results The search resulted in 3242 ongoing studies of which 829 studies were included. There are 134 different drug-based interventions being assessed in 463 clinical trials as treatment options. Seventy-two studies assessed preventive options of which 53 are drug-based prophylaxis and 19 assessed vaccines. Herbal medicines are being assessed in 79 studies; convalescent plasma therapy in 56 studies; stem cell based interventions in 42 studies; anesthesia-based interventions in 31 studies, machine-based interventions in 24 studies, mental health- based interventions in18 studies, rehabilitation based interventions in 12 studies and miscellaneous interventions in 32 studies. China accounts for 35% of all ongoing clinical studies followed by USA 23%, France 7%, Spain 3.3%,Canada 2%, multi-country studies account only for 1.5% (13) and other countries together account for 28%.Amongst the 463 studies assessing drug-based treatment options, studies that are funded by federal and academic institutions are 79.6%, pharmaceutical company funded studies are 15.11% and no funding information is available in 5.10%. The definitive outcomes like mortality are being assessed as primary outcome in 22.8% of the studies only and need for ventilator in 6.2% of the studies. Rest of the studies has primary outcomes such as clinical recovery (15.9%), viral clearance(17.4%), time to recovery (10.1%), oxygen improvement (5.6%), ICU admission (1.9%), lab and imaging(6.4%), adverse effects (5.3%) and symptom reduction(1.5%),no outcome reported(6.2%) which account for 71% of the studies. Amongst the pharmaceutical company funded drug-based studies, only 20% of the studies had mortality as the primary outcome. Only 5.5% of the ongoing clinical trials are specifically designed to assess the most vulnerable population like elderly, patients with comorbidities and cancer. The most common intervention being tested against COVID-19 are antimalarial medications with 105 clinical studies. Hydroxychloroquine is the most common drug being tested with 83 ongoing studies. Conclusion Multiple intervention based clinical studies against SARS-CoV-2 are being performed throughout the world with a high concentration of clinical trials in the developed world. There is a high concern that most of the studies maybe repetitive; elderly and patients with comorbidities are being underrepresented; definite endpoints like mortality are being assessed in only one-fifth of the studies.

negative: Vulnerable Immigrant Populations in the New York Metropolitan Area and COVID-19: Lessons Learned in the Epicenter of the Crisis The epicenter of the COVID-19 crisis since March 17, 2020—the New York metropolitan area—is home to some of the largest Latino immigrant communities in the nation. These communities have long faced barriers to health care access, challenges due to immigration status, and financial and labor instability. The COVID-19 pandemic has aggravated these existing issues in a vulnerable, often forgotten, immigrant community. It is challenging for this population to access public information regarding COVID-19 testing, treatment, and assistance programs because this information is seldom disseminated in Spanish and even less frequently in Portuguese. While long-term solutions will require time and changes to policy, some short-term measures can mitigate the current situation. The authors share their experience from Newark, New Jersey, where partnerships of public and private community-based organizations (CBOs) have been successful in establishing trust between the health care system and a fearful Latino community. The Ironbound Initiative, a student group at Rutgers New Jersey Medical School in Newark, New Jersey, has partnered with Mantena Global Care, a Brazilian CBO in Newark, to facilitate dissemination of COVID-19–relevant information. Medical student volunteers, removed from their clinical duties, serve as virtual patient navigators, using social media to reach community members with the goals of improving awareness of precautions to take during the pandemic and of increasing access to needed medical care. These students have collaborated with colleagues in other disciplines to provide necessary legal guidance to community members fearful of seeking care because of their immigration status. The authors urge other academic institutions across the country to recruit multidisciplinary teams of medical, health professional, and law students invested in their local communities and to empower students to partner with CBOs, immigrant community leaders, faith-based organizations, hospitals, and local authorities to support these vulnerable communities during this crisis.

negative: Hydroxychloroquine and covid-19 Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.

negative: Cardiovascular system and COVID-19: perspectives from a developing country A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the "heart and virus" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.

negative: SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus Here we report on the most recent updates on experimental drugs successfully em- ployed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxy- chloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experi- mental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this vi- rus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.

negative: COVID-19 pandemic control: balancing detection policy and lockdown intervention under ICU sustainability We consider here an extended SIR model, including several features of the recent COVID-19 outbreak: in particular the infected and recovered individuals can either be detected (+) or undetected (-) and we also integrate an intensive care unit (ICU) capacity. Our model enables a tractable quantitative analysis of the optimal policy for the control of the epidemic dynamics using both lockdown and detection intervention levers. With parametric specification based on literature on COVID-19, we investigate the sensitivities of various quantities on the optimal strategies, taking into account the subtle trade-off between the sanitary and the socio-economic cost of the pandemic, together with the limited capacity level of ICU. We identify the optimal lockdown policy as an intervention structured in 4 successive phases: First a quick and strong lockdown intervention to stop the exponential growth of the contagion; second a short transition phase to reduce the prevalence of the virus; third a long period with full ICU capacity and stable virus prevalence; finally a return to normal social interactions with disappearance of the virus. The optimal scenario hereby avoids the second wave of infection, provided the lockdown is released sufficiently slowly. We also provide optimal intervention measures with increasing ICU capacity, as well as optimization over the effort on detection of infectious and immune individuals. Whenever massive resources are introduced to detect infected individuals, the pressure on social distancing can be released, whereas the impact of detection of immune individuals reveals to be more moderate.

negative: Increase in COVID-19 cases and case-fatality and case-recovery rates in Europe: A cross-temporal meta-analysis The new coronavirus (COVID-19) infection reported in China in December 2019 has become a pandemic in a few weeks, affecting the entire world. In this respect, it is crucial to determine the case-increase, case-fatality, and case-recovery rates to control COVID-19. In this study, the case-increase, case-fatality, and case-recovery rates of COVID-19 in 36 European countries were analyzed with the meta-analysis method using data released by the health organizations and WHO. The data were obtained from the website of health organizations of 36 European countries and the website of WHO until 11 May 2020. The analyses were carried out on 1 744 704 COVID-19-diagnosed cases in 36 European countries. The case-increase, case-fatality and case-recovery rates of COVID-19 were calculated using 95% confidence intervals (95% CI), single-arm meta-analysis, cross-temporal meta-analysis, and meta-regression random-effects model. The standardized case-increase rate of COVID-19 is 5% (95% CI [0.040, 0.063]) and the average case-increase rate in European countries has started to decline by around 3% (95% CI [0.047, 0.083]) weekly. The countries with the highest rate of case increase are Belgium, Sweden, Russia, the Netherlands and the United Kingdom. Although the case-fatality rate of COVID-19 patients was 4.5% as of May 11 (95% CI [0.037-0.055]), this rate is 6.3% (95% CI [0.047, 0.083]) in standardized time (6th week). The case-recovery rates of patients are 46% (95% CI [0.376-0.547]). This study presents important results regarding the COVID-19 pandemic in Europe. Although the rate of increase in new COVID-19 cases has dropped, there is not much decline in the case-fatality rates and no increase in case-recovery rates. The case-fatality rate of COVID-19 in Europe was estimated to be in the range of 4% to 4.5% and a minimum of 4 weeks (as of 11 May) is expected to have the figure below 1% in a country with an average case-increase rate. Monitoring case fatalities in Belgium, the Netherlands and Sweden, and treatment successes in Germany and Austria play a role of utmost importance.

negative: SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain in the host population. In turn, the virus can never completely eliminate the host population, because evolutionarily such an event is a dead end for the virus as an obligate intracellular parasite. A certain existential balance exists in the virus-host relationship. Against this backdrop, viral epidemics and pandemics only become manifest and egregious to human beings when tens and hundreds of thousands of people die and the question emerges what caused the high mortality peaks on the death chart. The answer seems clear; the emerging strain of the virus is new to the host population, and new mutations of the virus and natural selection will lead to a survival of only genetically resistant individuals in a host population. The dangers inherent to a novel virus are due to new features generally inthe molecular structure of proteins, which enable the virus to infect the cells of the host organism more intensively, dramatically challenging host immunity, and thus be transmitted more readily in the host population. In this article, we will concentrate on the facts currently available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused COVID-19 (coronavirus disease 2019) pandemic and try to predict its development and consequences based on the virus-host relationship. In fact, only two scenarios will occur simultaneously in the very near future: people who are genetically resistant to the virus will get sick, recover, and develop immunity, while people who are sensitive to the virus will need drugs and vaccines, which will have to be researched and developed if they are to recover. If the pandemic does not stop, in a few decades it is anticipated that SARS-CoV-2 will become as safe as the four non-severe acute respiratory syndrome human coronaviruses (HCoV-NL63, HCoV-HKU1, HCoV-OC43, and HCoV-229E) currently circulating but causing low mortality in the human population.

negative: A Viewpoint on Angiotensin-Converting Enzyme 2, Anti-Hypertensives and Coronavirus Disease 2019 (COVID-19)

negative: Passive antibody therapy in COVID-19 For over a century, transfusion of convalescent plasma from recovered individuals has been tried as a therapeutic approach when a novel pathogen emerges. As the world awaits SARS-CoV-2 vaccines to be tested and safely deployed, the rapidity with which antiviral monoclonal antibodies can be isolated and engineered offers an attractive alternative option for passive immunization.

negative: COVID-19 Community Stabilization and Sustainability Framework: An Integration of the Maslow Hierarchy of Needs and Social Determinants of Health All levels of government are authorized to apply coronavirus disease 2019 (COVID-19) protection measures; however, they must consider how and when to ease lockdown restrictions to limit long-term societal harm and societal instability. Leaders that use a well-considered framework with an incremental approach will be able to gradually restart society while simultaneously maintaining the public health benefits achieved through lockdown measures. Economically vulnerable populations cannot endure long-term lockdown, and most countries lack the ability to maintain a full nationwide relief operation. Decision-makers need to understand this risk and how the Maslow hierarchy of needs and the social determinants of health can guide whole of society policies. Aligning decisions with societal needs will help ensure all segments of society are catered to and met while managing the crisis. This must inform the process of incremental easing of lockdowns to facilitate the resumption of community foundations, such as commerce, education, and employment in a manner that protects those most vulnerable to COVID-19. This study proposes a framework for identifying a path forward. It reflects on baseline requirements, regulations and recommendations, triggers, and implementation. Those desiring a successful recovery from the COVID-19 pandemic need to adopt an evidence-based framework now to ensure community stabilization and sustainability.

negative: Letter to the Editor ”The Battle of Humans and COVID-19: A War without Smoke”

negative: Child with liver transplant recovers from COVID-19 infection. A case report Abstract We present the case of a 55-month-old girl who recovered from coronavirus disease 2019 (COVID-19) infection 5 months after undergoing liver transplantation; she had a co-infection with Epstein–Barr virus (EBV). To the best of our knowledge, this is the first case report of a COVID-19 infection in a pediatric patient with liver transplantation. Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.

negative: COVID-19 and spinal cord injury and disease: results of an international survey STUDY DESIGN: An online survey. OBJECTIVES: To query the international spinal cord medicine community’s engagement with and response to the novel coronavirus (COVID-19) pandemic and to assess pandemic-specific information needs and patient concerns. SETTING: An international collaboration of authors and participants. METHODS: Two near-identical surveys (one English and one Spanish language) were distributed via the internet. Responses from those questions shared between the surveys were pooled then analyzed; four questions’ responses (those not shared) were analyzed separately. RESULTS: A total of 783 responses were submitted from six continents. Few participants (5.8%) had tested their outpatients with SCI/D for COVID-19; only 4.4% reported having a patient with SCI/D with the virus. Of respondents who worked at an inpatient facility, 53.3% reported that only individuals with symptoms were being screened and 29.9% said that no screening was occurring. Participants relayed several concerns offered by their patients with SCI/D, including vulnerability to infection (76.9%) and fragility of caretaker supply (42%), and those living in countries with guaranteed health care were more likely to report widespread availability of COVID-19 testing than were those living in countries without universal care, χ(2) (3, N = 625) = 46.259, p < 0.001. CONCLUSION: There is substantial variability in the rehabilitation medicine community in COVID-19 screening practices and availability of screening kits. People living with SCI/D are expressing legitimate and real concerns about their vulnerability to COVID-19. More and rapid work is needed to address these concerns and to standardize best-practice protocols throughout the rehabilitation community.

negative: Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future.

negative: The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID‐19): A Chinese perspective 2019 novel coronavirus (SARS‐CoV‐2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID‐19). However, SARS‐CoV‐2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID‐19 in China to better understand the transmission and diagnosis regarding this infectious disease.

negative: The race to find a SARS-CoV-2 drug can only be won by a few chosen drugs: a systematic review of registers of clinical trials of drugs aimed at preventing or treating COVID-19 Considering the massive amount of clinical trial registers aimed to find effective drugs for the prevention and treatment of COVID-19, it is challenging to have a comprehensive view of which drugs are being studied more extensively and when is expected that we will have consistent results regarding their effectiveness. This systematic review included all clinical trials on pharmacological therapy related to COVID-19 and SARS-CoV-2 registered at the International Clinical Trials Registry Platform (WHO-ICTRP) up to April 22, 2020. Clinical trials characteristics (country, design, sample size, main outcomes, expected completion data, type of participants, length of the interventions, main outcomes). How many trials and he accumulated sample size by drug or combination of drugs, and by month in 2020 was depicted. We identified 412 clinical trials registers addressing the effect of pharmacological treatments on COVID-19, predominantly from Asia and Europe (42.2% and 31.1% of clinical trials registers, respectively). The most main outcomes studied were clinical recovery (54.4% of the clinical trials registers, respiratory recovery (28.2%) mortality (27.4%), viral load/negativity (20.4%). During 2020, a huge amount of clinical trials are expected to be completed: 41 trials (60,366 participants) using hydroxychloroquine, 20 trials (1,588 participants) using plasma, 18 trials (6,830 participants) using chloroquine, 12 trials (9,938 participants using lopinavir/ritonavir, 11 trials (1,250 participants) using favipiravir, 10 trials ( 2,175 participants) using tocilizumab and 6 trials (13,540 participants) using Remdesivir. The distribution of the number of registered clinical trials among the different therapeutic options leads to an excess of sample size for some and a lack for others. Our data allow us to conclude that by the end of June we will have results of almost 20 trials involving 40000 patients for hydroxychloroquine and 5 trials with 4500 patients for remdesivir; however, low statistical power is expected from the 9 clinical trials testing the efficacy of favipiravir or the 5 testing tocilizumab, since they will recruit less than 1000 patients each one.

negative: The D model for deaths by COVID-19 We present a simple analytical model to describe the fast increase of deaths produced by the corona virus (COVID-19) infections. The 'D' (deaths) model comes from a simplified version of the SIR (susceptible-infected-recovered) model known as SI model. It assumes that there is no recovery. In that case the dynamical equations can be solved analytically and the result is extended to describe the D-function that depends on three parameters that we can fit to the data. Results for the data from Spain, Italy and China are presented. The model is validated by comparing with the data of deaths in China, which are well described. This allows to make predictions for the development of the disease in Spain and Italy.

negative: Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1–7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1–7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined.

negative: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management and Infection Control in a Radiology Department Abstract Objective To describe the strategy and the emergency management and infection control procedure of our radiology department during the coronavirus disease 2019 (COVID-19) outbreak. Methods We set up emergency management and sensing control teams. The team formulated various measures: reconfiguration of the radiology department, personal protection and training of staff, examination procedures for patients suspected of or confirmed with COVID-19 as well as patients without an exposure history or symptoms. Those with suspected or confirmed COVID-19 infection were scanned in the designated fever-CT unit. Results From January 21, 2020, to March 9, 2020, 3,083 people suspected or confirmed to be infected with COVID-19 underwent fever-CT examinations. Including initial examinations and re-examinations, the total number of fever-CT examinations numbered 3,340. As a result of our precautions, none of the staff of the radiology department were infected with COVID-19. Conclusion Strategic planning and adequate protections can help protect patients and staff against a highly infectious disease while maintaining function at a high-volume capacity.

negative: Tracing DAY-ZERO and Forecasting the Fade out of the COVID-19 Outbreak in Lombardy, Italy: A Compartmental Modelling and Numerical Optimization Approach. Italy currently constitutes the epicenter of the novel coronavirus disease (COVID-19) pandemic, having surpassed China's death toll. The disease is sweeping through Lombardy, which remains in lockdown since the 8th of March. As of the same day, the isolation measures taken in Lombardy have been extended to the entire country. Here, we provide estimates for: (a) the DAY-ZERO of the outbreak in Lombardy, Italy; (b) the actual number of exposed/infected cases in the total population; (c) the basic reproduction number (R0); (d) the "effective" per-day disease transmission; and, importantly, (e) a forecast for the fade out of the outbreak, on the basis of the COVID-19 Community Mobility Reports released by Google on March 29. Methods. To deal with the uncertainty in the number of actual exposed/ infected cases in the total population, we address a compartmental Susceptible/ Exposed/ Infectious/ Recovered/ Dead (SEIRD) model with two compartments of infectious persons: one modelling the total cases in the population and another modelling the confirmed cases. The parameters of the model corresponding to the recovery period, the time from the onset of symptoms to death, the case fatality ratio, and the time from exposure to the time that an individual starts to be infectious, have been set as reported from clinical studies on COVID-19. For the estimation of the DAY-ZERO of the outbreak in Lombardy, as well as of the ``effective" per-day transmission rate for which no clinical data are available, we have used the SEIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March, the lockdown day of Lombardy and of all Italy. This was accomplished by solving a mixed-integer optimization problem with the aid of genetic algorithms. Based on the computed values, we also provide an estimation of the basic reproduction number $R_0$. Furthermore, based on an estimation for the reduction in the "effective" transmission rate of the disease as of March 8 that reflects the suspension of almost all activities in Italy, we ran the simulator to forecast the fade out of the epidemic. For this purpose, we considered the reduction in mobility in Lombardy as released on March 29 by Google COVID-19 Community Mobility Reports, the effect of social distancing, and the draconian measures taken by the government on March 20 and March 21, 2020. Results. Based on the proposed methodological procedure, we estimated that the DAY-ZERO was most likely between January 5 and January 23 with the most probable date the 15th of January 2020. The actual cumulative number of exposed cases in the total population in Lombardy on March 8 was of the order of 15 times the confirmed cumulative number of infected cases. The "effective" per-day disease transmission rate for the period until March 8 was found to be 0.686 (95% CI:0.660, 0.713), while the basic reproduction number R0 was found to be 4.51 (95% CI: 4.14, 4.90). Importantly, simulations show that the COVID-19 pandemic in Lombardy is expected to fade out by the end of May - early June, 2020, if the draconian, as of March 20 and March 21, measures are maintained.

negative: Correlation of High-Resolution CT, Symptoms, and Pulmonary Function in Patients During Recovery From Severe Acute Respiratory Syndrome Study objectives: Little is known of the nature of the recovery period after severe acute respiratory syndrome (SARS) infection. We hypothesized that structural changes of the lung might correlate with symptoms and pulmonary function. To answer this question, we correlate findings of high-resolution CT (HRCT) with dyspnea scores and results of pulmonary function tests in patients during recovery from SARS. Design: Retrospective follow-up cohort study. Setting: University hospital. Patients: Nineteen patients who recovered from SARS-related hospitalization. Measurements: The study included HRCT scores (0 to 100), dyspnea scores (1 to 4), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (Dlco). Results: The interval between hospital discharge and HRCT study or functional assessment was 31.2 ± 4.8 days (range, 25 to 38 days) [mean ± SD]. All patients had HRCT abnormalities and were assigned to two groups: ground-glass opacity (GGO) only (n = 7, 36.8%) and GGO with fibrosis (GGO+F) [n = 12, 63.2%]. Most patients (16 of 19, 84.2%) had no zonal predominance. HRCT scores correlated well with dyspnea scores (r = 0.78, p < 0.01) and with a variety of pulmonary functional variables, with Dlco being the most significant (r = − 0.923, p < 0.001). Compared with the GGO group, the GGO+F group showed significantly lower FEV1, FVC, total lung capacity, residual volume, and Dlco. Conclusions: HRCT findings correlate well with functional studies and clinical symptoms during recovery from SARS. Longer-term follow-up studies in a larger cohort of patients should be performed to investigate the clinical outcome of recovered SARS patients.

negative: Presence of SARS-Coronavirus-2 RNA in Sewage and Correlation with Reported COVID-19 Prevalence in the Early Stage of the Epidemic in The Netherlands [Image: see text] In the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 RNA was present in sewage during the emergence of COVID-19 in The Netherlands, sewage samples of six cities and the airport were tested using four qRT-PCR assays, three targeting the nucleocapsid gene (N1–N3) and one the envelope gene (E). No SARS-CoV-2 RNA was detected on February 6, 3 weeks before the first Dutch case was reported. On March 4/5, one or more gene fragments were detected in sewage of three sites, in concentrations of 2.6–30 gene copies per mL. In Amersfoort, N3 was detected in sewage 6 days before the first cases were reported. As the prevalence of COVID-19 in these cities increased in March, the RNA signal detected by each qRT-PCR assay increased, for N1–N3 up to 790–2200 gene copies per mL. This increase correlated significantly with the increase in reported COVID-19 prevalence. The detection of the virus RNA in sewage, even when the COVID-19 prevalence is low, and the correlation between concentration in sewage and reported prevalence of COVID-19, indicate that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.

negative: Coronavirus disease 2019 and transplantation: The combination of lopinavir/ritonavir and hydroxychloroquine is responsible for excessive tacrolimus trough level and unfavorable outcome The ongoing outbreak of coronavirus disease 2019 (COVID‐19) first reported in Wuhan has been declared global public health emergency and a pandemic by the World Health Organization. Faced with this novel coronavirus, scientists have been trying to use drugs that have not been validated by rigorous clinical trials, such as lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ). These drugs may be used tentatively for general population with COVID‐19, but for solid organ transplant (SOT) recipients with long‐term immunosuppressive therapy and drug‐related metabolic diseases, antiviral drugs should be chosen with particular care. Notably, the elderly SOT patients commonly suffer from liver and kidney dysfunction of varying degrees, resulting in worse drug metabolism.

negative: Severe COVID-19 After Recent Heart Transplantation Complicated by Allograft Dysfunction Abstract A 50-year-old male presented with atrial flutter 25 days after heart and kidney transplantation. Rejection was excluded, however, he developed severe COVID-19 with cardiac allograft dysfunction. Despite continued corticosteroids and tacrolimus, he remained aviremic. Respiratory and myocardial function recovered after a week of mechanical ventilation. The cardiomyopathy was stress induced.

negative: The management of adult appendicitis during the COVID-19 pandemic: an interim analysis of a UK cohort study BACKGROUND: Acute appendicitis (AA) is the most common general surgical emergency. Early laparoscopic appendicectomy is the gold-standard management. SARS-CoV-2 (COVID-19) brought concerns of increased perioperative mortality and spread of infection during aerosol generating procedures: as a consequence, conservative management was advised, and open appendicectomy recommended when surgery was unavoidable. This study describes the impact of the first weeks of the pandemic on the management of AA in the United Kingdom (UK). METHODS: Patients 18 years or older, diagnosed clinically and/or radiologically with AA were eligible for inclusion in this prospective, multicentre cohort study. Data was collected from 23rd March 2020 (beginning of the UK Government lockdown) to 1st May 2020 and included: patient demographics, COVID status; initial management (operative and conservative); length of stay; and 30-day complications. Analysis was performed on the first 500 cases with 30-day follow-up. RESULTS: The patient cohort consisted of 500 patients from 48 sites. The median age of this cohort was 35 [26–49.75] years and 233 (47%) of patients were female. Two hundred and seventy-one (54%) patients were initially treated conservatively; with only 26 (10%) cases progressing to an operation. Operative interventions were performed laparoscopically in 44% (93/211). Median length of hospital stay was significantly reduced in the conservatively managed group (2 [IQR 1–4] days vs. 3 [2–4], p < 0.001). At 30 days, complications were significantly higher in the operative group (p < 0.001), with no deaths in any group. Of the 159 (32%) patients tested for COVID-19 on admission, only 6 (4%) were positive. CONCLUSION: COVID-19 has changed the management of acute appendicitis in the UK, with non-operative management shown to be safe and effective in the short-term. Antibiotics should be considered as the first line during the pandemic and perhaps beyond.

negative: Coronavirus spreads The deadly virus that emerged in Wuhan, China, may be much more contagious than initially thought. Jessica Hamzelou reports

negative: Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment. Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.

negative: Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019 There has been a global outbreak of coronavirus disease 2019 (COVID‐19) since December 2019. In clinical practice, not only fever and respiratory tract symptoms but also multiple organ symptoms are observed in patients diagnosed with COVID‐19. Herein, we report a rare case of a patient diagnosed with COVID‐19 who manifested with concomitant neurological symptoms. The patient developed fever and respiratory symptoms at disease onset, followed by muscle soreness, and subsequently altered consciousness and psychiatric symptoms, with positive signs based on neurological examination. The patient tested positive for the severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) nucleic acid (throat swab). Further, chest computed tomography (CT) revealed typical COVID‐19 findings, and head CT did not reveal significant abnormalities. The patient recovered after treatment and was discharged. This rare case indicates that SARS‐CoV‐2 can invade the central nervous system, thus causing neurological symptoms and signs. This article is protected by copyright. All rights reserved.

negative: Pathophysiology of COVID-19: Why Children Fare Better than Adults? The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.

negative: Immunity after COVID-19: protection or sensitization ? Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.

negative: Assessment of SARS-CoV-2 in human semen - a cohort study OBJECTIVE: To investigate the presence of viral RNA in human semen of severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) recovered and positive patients and to evaluate its presence and relevance on semen parameters. DESIGN: Pilot cohort study SETTING: University hospital PATIENTS: 34 adult males were distributed into a) patients in convalescence (patients with confirmed SARS-CoV-2 infection in pharyngeal swab by RT-PCR and/or antibodies), b) negative control group (no antibodies) and c) patients with an acute infection (detection of SARS-CoV-2 in pharyngeal swab). INTERVENTION: Semen and a blood sample were collected from each individual. MAIN OUTCOME MEASURES: Analysis of semen quality according to the WHO standards. Detection of SARS-CoV-2 by RT-PCR in the native semen sample and after density gradient preparation. Confirmation of Immunoglobulin (Ig)-A und Ig-G antibodies in the blood. RESULTS: 18 semen samples from recovered males were obtained 8 to 54 days after absence of symptoms, 14 samples from controls and 2 samples from patients with an active COVID-19 infection. No RNA was detected by RT-PCR in the semen including semen samples from two patients with an acute COVID-19 infection. Subjects with a moderate infection showed an impairment of sperm quality. CONCLUSION: A mild COVID-19 infection is not likely to affect testis and epididymis function, whereas semen parameters did seem impaired after a moderate infection . SARS-CoV-2 RNA could not be detected in semen of recovered and acute COVID-19 positive males. This suggests no viral transmission during sexual contact and assisted reproductive techniques (ART), however, further data need to be obtained.

negative: Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms but there is a little evidence-based published material on the neurological manifestations of COVID-19. The purpose of this article is to review the spectrum of the various neurological manifestations and underlying associated pathophysiology in COVID-19 patients. Method: We conducted a review of the various case reports and retrospective clinical studies published on the neurological manifestations, associated literature, and related pathophysiology of COVID-19 using PUBMED and subsequent proceedings. A total of 118 articles were thoroughly reviewed in order to highlight the plausible spectrum of neurological manifestations of COVID 19. Every article was either based on descriptive analysis, clinical scenarios, correspondence, and editorials emphasizing the neurological manifestations either directly or indirectly. We then tried to highlight the significant plausible manifestations and complications that could be related to the pandemic. With little known about the dynamics and the presentation spectrum of the virus apart from the respiratory symptoms, this area needs further consideration. Conclusion: The neurological manifestations associated with COVID-19 such as Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barré Syndrome (GBS) are of great concern. But in the presence of life-threatening abnormal vitals in severely ill COVID-19 patients, these are not usually underscored. There is a need to diagnose these manifestations at the earliest to limit long term sequelae. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from cerebrospinal fluid or brain tissues of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.

negative: Respiratory and pulmonary complications in head and neck cancer patients: Evidence‐based review for the COVID‐19 era BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID‐19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID‐19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long‐term management and health of these patients.

negative: The relationships between health anxiety, online health information seeking, and cyberchondria: Systematic review and meta-analysis. BACKGROUND Cyberchondria refers to an abnormal behavioral pattern in which excessive or repeated online searches for health-related information are distressing or anxiety-provoking. Health anxiety has been found to be associated with both online health information seeking and cyberchondria. The aims of the present systematic review and meta-analysis were to examine the magnitude of these associations and identify any moderator variables. METHODS A systematic literature search was performed across several databases (PsycINFO, PubMed, Embase) and reference lists of included studies. RESULTS Twenty studies were included across two independent meta-analyses, with 7373 participants. Random effects meta-analyses showed that there was a positive correlation between health anxiety and online health information seeking [r = 0.34, 95% CI (0.20, 0.48), p < .0001], and between health anxiety and cyberchondria [r = 0.62, 95% CI (0.52, 0.71), p < .0001]. A meta-regression indicated that the age of study participants [Q(1) = 4.58, p = .03] was partly responsible for the heterogeneity found for the relationship between health anxiety and cyberchondria. LIMITATIONS The generalizability and validity of our findings are restricted by the methodological limitations of the primary studies, namely, an over-reliance on a single measure of cyberchondria, the Cyberchondria Severity Scale. CONCLUSIONS Our review found a positive correlation between health anxiety and online health information seeking, and between health anxiety and cyberchondria. Further research should aim to explore the contexts for these associations as well as address the identified limitations of the extant literature.

negative: Clinical progression of patients with COVID-19 in Shanghai, China Summary Background Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. Methods In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. Results Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2–7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12–20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8–11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10–12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. Conclusions The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

negative: Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19) Abstract Objectives To investigate the widely concerned issue about positive real-time reverse transcription polymerase chain reaction (RT-PCR) test results after discharge in patients recovered from coronavirus disease 2019 (COVID-19). Methods We identified seven cases of COVID-19 who was readmitted to hospital because of positive RT-PCR after discharge, including three pediatrics and four young adult patients. Results Six patients had positive rectal swabs but negative throat swabs, and one patient had positive throat swabs. All the patients continued to be asymptomatic and had unchanged chest computed tomography from previous images. The time from hospital discharge to positive RT-PCR after recovery was 7–11 days. The time from positive to negative rectal swabs was 5-23 days. Conclusion The study might suggest the positive RT-PCR after recovery did not mean disease relapse or virus reinfection. Adding RT-PCR test of rectal swabs to the criteria for discharge or discontinuation of quarantine might be necessary.

negative: To recover faster from Covid-19, open up: Managerial implications from an open innovation perspective Abstract Covid-19 has severely tested our public health systems. Recovering from Covid-19 will soon test our economic systems. Innovation will have an important role to play in recovering from the aftermath of the coronavirus. This article discusses both how to manage innovation as part of that recovery, and also derives some lessons from how we have responded to the virus so far, and what those lessons imply for managing innovation during the recovery.

negative: Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. BACKGROUND Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI. METHODS In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes. RESULTS We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI. CONCLUSIONS Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.

negative: Comparative Global Epidemiological Investigation of SARS-CoV-2 and SARS-CoV Diseases Using Meta-MUMS Tool Through Incidence, Mortality, and Recovery Rates COVID-19 is a novel coronavirus that was reported by the world health organization in late December 2019. As an unexplained respiratory disease epidemic, which is similar to respiratory syndrome coronavirus SARS-CoV, it rapidly spread all over the world. The study aims to compare several parameters of COVID-19 and SARS-CoV infectious diseases in terms of incidence, mortality, and recovery rates. The publicly available dataset Worldometer (extracted on April 5, 2020) confirmed by WHO report was available for meta-analysis purposes using the Meta-MUMS tool. And, the reported outcomes of the analysis used a random-effects model to evaluate the event rate, and risk ratios thorough subgroup analysis forest plots. Seventeen countries for COVID-19 and eight countries of SARS infections, including COVID-19 group n = 1124243, and SARS-CoV group n = 8346, were analyzed. In this meta-analysis, a random effect model of relations of incidence, mortality, and recovery rates of COVID-19 and SARS world infections were determined. The meta-analysis and forest plots of two viral world infections showed that the incidence rate of COVID-19 infection is more than SARS infections, while recovery and mortality event rates of SARS-CoV are more than COVID-19 infection. And subgroup analysis showed that the mortality and recovery rates were higher in both SARS-CoV wand COVID-19 in comparison to incidence and mortality rates, respectively. In conclusion, the meta-analysis approach on the abovementioned dataset revealed the epidemiological and statistical analyses for comparing COVID-19 and SARS-CoV outbreaks.

negative: 62(ND) ASMS Conference on Mass Spectrometry and Allied Topics

negative: Considerations for Postacute Rehabilitation for Survivors of COVID-19 Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question “What rehabilitation services do survivors of COVID-19 require?” The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.

negative: Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19 Background: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. Methods: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). Results: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). Conclusions: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

negative: Transplantation of ACE2(-) Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b(mid) regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2(-) and TMPRSS2(-) which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

negative: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

negative: COVID-19: health literacy is an underestimated problem

negative: Abdominal Pain: A Real Challenge in Novel COVID-19 Infection COVID-19 (coronavirus disease 19) is an infectious disease caused by coronavirus 2019-nCoV. Since its detection in China at the end of 2019, the novel coronavirus has rapidly spread throughout the world and has caused an international public health emergency. The most common manifestation is flu-like symptoms. Mild infections usually improve within a few days, but COVID-19 can cause severe pneumonia with acute respiratory distress syndrome and death. Gastrointestinal symptoms are less common but possible and more difficult to recognize as part of a COVID-19 syndrome. In line with the current opinion of the WHO, we strongly believe that preventive measures and early diagnosis of COVID-19 are crucial to interrupt virus spread and avoid local outbreaks. We report the cases of COVID-19 patients admitted to our Emergency Department who complained of gastrointestinal symptoms at admission. LEARNING POINTS: The novel COVID-19 infection is a severe public health problem which is causing an increasing number of deaths worldwide. Although uncommon, there may be a relationship between gastrointestinal symptoms and COVID-19, as reported in recent studies. Early detection and isolation of patients with COVID-19 infection is the only way to control and limit the global spread of this virus.

negative: Interventional oncology at the time of COVID-19 pandemic: problems and solutions Abstract The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.

negative: Cardiovascular Pharmacology in the Time of COVID-19: A Focus on Angiotensin-Converting Enzyme 2 Coronavirus disease-2019 (COVID-19) has emerged as a pandemic affecting millions of adults. Severe acute respiratory syndrome coronavirus-2019 (SARS-CoV-2), the causative virus of COVID-19, infects host cells through angiotensin-converting enzyme 2 (ACE2). Preclinical models suggest that ACE2 upregulation confers protective effects in acute lung injury. In addition, renin-angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease outcomes, but may increase ACE2 levels. We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology, as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin-angiotensin-aldosterone system inhibitor therapy.

negative: Serological signatures of SARS-CoV-2 infection: Implications for antibody-based diagnostics Background The antibody response generated following infection with SARS-CoV-2 is expected to decline over time. This may cause individuals with confirmed SARS-CoV-2 infection to test negative according to serological diagnostic tests in the months and years following symptom onset. Methods A multiplex serological assay was developed to measure IgG and IgM antibody responses to four SARS-CoV-2 Spike (S) antigens: spike trimeric ectodomain (Stri), its receptor-binding domain (RBD), spike subunit 1 (S1), and spike subunit 2 (S2). Antibody responses were measured in serum samples from patients in French hospitals with RT-qPCR confirmed infection (n = 259), and negative control serum samples collected before the start of the SARS-CoV-2 epidemic in 2019 (n = 335). The multiplex antibody data was used to train a random forests algorithm for classifying individuals with previous SARS-CoV-2 infection. A mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the potential sensitivity and classification performance of serological diagnostics during the first year following symptom onset. Results IgG antibody responses to one S antigen identified individuals with previous RT-qPCR confirmed SARS-CoV-2 infection with 90.3% sensitivity (95% confidence interval (CI); 86.1%, 93.4%) and 99.1% specificity (95% CI; 97.4%, 99.7%). Using a serological signature of IgG to four antigens, it was possible to identify infected individuals with 96.1% sensitivity (95% CI; 93.0%, 97.9%) and 99.1% specificity (95% CI; 97.4%, 99.7%). Antibody responses to SARS-CoV-2 increase rapidly 1-2 weeks after symptom onset, with antibody responses predicted to peak within 2-4 weeks. Informed by prior data from other coronaviruses, one year following symptom onset antibody responses are predicted to decay by approximately 60% from the peak response. Depending on the selection of sero-positivity cutoff, we estimate that the sensitivity of serological diagnostics may reduce to 56%-97% after six months, and to 49%-93% after one year. Conclusion Serological signatures based on antibody responses to multiple antigens can provide more accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. Changes in antibody levels over time may cause reductions in the sensitivity of serological diagnostics leading to an underestimation of sero-prevalence. It is essential that data continue to be collected to evaluate this potential risk.

negative: Management strategies in a SEIR model of COVID 19 community spread The 2019 Novel Corona virus infection (COVID-19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID-19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. We construct and analyze here one first step: that of adapting a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID-19, as it spreads in an age-heterogeneous community. We analyze the current management strategy of the epidemic course (travel bans, service closures and interruptions, social distancing). We generate predictions, and assess the efficiency of these control measures, in the context in which their sustainability is currently being questioned.

negative: Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as “Remdesivir” or ‘GS-5734″ AND “COVID-19” or “SARS-CoV-2” and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.

negative: Public pensions and unmet medical need among older people: cross-national analysis of 16 European countries, 2004–2010 BACKGROUND: Since the onset of the Great Recession in Europe, unmet need for medical care has been increasing, especially in persons aged 65 or older. It is possible that public pensions buffer access to healthcare in older persons during times of economic crisis, but to our knowledge, this has not been tested empirically in Europe. METHODS: We integrated panel data on 16 European countries for years 2004–2010 with indicators of public pension, unemployment insurance and sickness insurance entitlement from the Comparative Welfare Entitlements Dataset and unmet need (due to cost) prevalence rates from EuroStat 2014 edition. Using country-level fixed-effects regression models, we evaluate whether greater public pension entitlement, which helps reduce old-age poverty, reduces the prevalence of unmet medical need in older persons and whether it reduces inequalities in unmet medical need across the income distribution. RESULTS: We found that each 1-unit increase in public pension entitlement is associated with a 1.11 percentage-point decline in unmet medical need due to cost among over 65s (95% CI −0.55 to −1.66). This association is strongest for the lowest income quintile (1.65 percentage points, 95% CI −1.19 to −2.10). Importantly, we found consistent evidence that out-of-pocket payments were linked with greater unmet needs, but that this association was mitigated by greater public pension entitlement (β=−1.21 percentage points, 95% CI −0.37 to −2.06). CONCLUSIONS: Greater public pension entitlement plays a crucial role in reducing inequalities in unmet medical need among older persons, especially in healthcare systems which rely heavily on out-of-pocket payments.

negative: Perspectives for the use of therapeutic Botulinum toxin as a multifaceted candidate drug to attenuate COVID-19 Abstract The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While the lungs are the primary target for the SARS-CoV-2-mediated pathological consequence, SARS-CoV-2 appear to invade the brain and cause neurological deficits. In the later stage, COVID-19 can progress to pneumonia, acute respiratory failure, neurological deficits and multi-organ dysfunctions leading to death. Though a significant portion of SARS-CoV-2 infected individuals has been recovering from pathological symptoms, the impact of the COVID-19 on the structural and functional properties of the lungs, heart, brain and other organs at the post-recovery state remains unknown. Presently, there is an urgent need for a remedial measure to combat this devastating COVID-19. Botulinum toxins (BoNTs) are potent neurotoxins that can induce paralysis of muscle and acute respiratory arrest in human. However, a mild dose of the purified form of BoNT has been known to attenuate chronic cough, dyspnoea, pneumonia, acute respiratory failure, abnormal circulation, cardiac defects and various neurological deficits that have been recognised as the prominent clinical symptoms of COVID-19. Considering the fact, this review article provides 1) an overview on the SARS-CoV-2 mediated pathological impact on the lungs, heart and brain, 2) signifies the therapeutic uses of BoNTs against pulmonary failure, cardiac arrest and neurological deficits, and 3) emphasize the rationality for the possible use of BoNT to prevent SARS-CoV-2 infection and manage COVID-19.

negative: Expert recommendations on blood purification treatment protocol for patients with severe COVID-19 Recommendation and consensus Abstract Coronavirus disease (COVID-19) was first diagnosed in Wuhan in December 2019. The World Health Organization defined the subsequent outbreak of COVID-19 worldwide as a public health emergency of international concern. Epidemiological data indicate that at least 20% of COVID-19 patients have severe disease. In addition to impairment of the respiratory system, acute kidney injury (AKI) is a major complication. Immune damage mediated by cytokine storms and concomitant AKI is a key factor for poor prognosis. Based on previous experience of blood purification for patients with severe acute respiratory syndrome and Middle East respiratory syndrome combined with clinical front-line practice, we developed a blood purification protocol for patients with severe COVID-19. This protocol is divided into four major steps. The first step is to assess whether patients with severe COVID-19 require blood purification. The second step is to prescribe a blood purification treatment for patients with COVID-19. The third step is to monitor and adjust parameters of blood purification. The fourth step is to evaluate the timing of discontinuation of blood purification. It is expected that blood purification will play a key role in effectively reducing the mortality of patients with severe COVID-19 through the standardized implementation of the present protocol.

negative: The Effect of Large-Scale Anti-Contagion Policies on the Coronavirus (COVID-19) Pandemic Governments around the world are responding to the novel coronavirus (COVID-19) pandemic with unprecedented policies designed to slow the growth rate of infections. Many actions, such as closing schools and restricting populations to their homes, impose large and visible costs on society. In contrast, the benefits of these policies, in the form of infections that did not occur, cannot be directly observed and are currently understood through process-based simulations. Here, we compile new data on 1,659 local, regional, and national anti-contagion policies recently deployed in the ongoing pandemic across localities in China, South Korea, Iran, Italy, France, and the United States (US). We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of any policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of roughly 42% per day. We find that anti-contagion policies collectively have had significant effects slowing this growth. Our results suggest that similar policies may have different impacts on different populations, but we obtain consistent evidence that the policy packages now deployed are achieving large, beneficial, and measurable health outcomes. We estimate that, to date, current policies have already prevented or delayed on the order of 62 million infections across these six countries. These findings may help inform whether or when these ongoing policies should be lifted or intensified, and they can support decision-making in the other 180+ countries where COVID-19 has been reported.

negative: Information Seeking Responses to News of Local COVID-19 Cases: Evidence from Internet Search Data The novel coronavirus (COVID-19) outbreak is a global pandemic with community circulation in many countries, including the U.S. where every state is reporting confirmed cases. The course of this pandemic will be largely shaped by how governments enact timely policies, disseminate the information, and most importantly, how the public reacts to them. Here, we examine informationseeking responses to the first COVID-19 case public announcement in a state. By using an eventstudy framework, we show that such news increases collective attention to the crisis right away, but the elevated level of attention is short-lived, even though the initial announcements were followed by increasingly strong measures. We find that people respond to the first report of COVID-19 in their state by immediately seeking information about COVID-19, as measured by searches for coronavirus, coronavirus symptoms and hand sanitizer. On the other hand, searches for information regarding community level policies (e.g., quarantine, school closures, testing), or personal health strategies (e.g., masks, grocery delivery, over-the-counter medications) do not appear to be immediately triggered by first reports. These results are encouraging given our study period is relatively early in the epidemic and more elaborate policy responses were not yet part of the public discourse. Further analysis will track evolving patterns of responses to subsequent flows of public information.

negative: Challenge for Rehabilitation After Hospitalization for COVID-19

negative: Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19

negative: Management and Treatment of COVID-19: The Chinese Experience Abstract With over 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. The objective of this paper is to critically review the available evidence regarding the lessons learned from the Chinese experience regarding COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hebei and the rest of the country, as well as closure of all schools and non-essential businesses. Other measures included the rapid construction of two new hospitals and the establishment of Fangcang shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin and convalescent plasma infusions. These measures appeared to provide only moderate success. While some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well-controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers and contacts, and early implementation of quarantine measures with an organized, proactive and unified strategy at a national level. Delays result in significantly higher death tolls.

negative: Risk-adapted Treatment Strategy For COVID-19 Patients BACKGROUND: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease (COVID-19). The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19. METHODS: We collected the medical records of 55 COVID-19 patients for analysis. We divided these patients into mild, moderate and severe groups, and risk-adapted treatment approaches were given according to the illness severity. RESULTS: Twelve patients were in mild group and 22 were in moderate group (non-severe group, n = 34), and 21 patients were in severe group. At the end of the first two weeks after admission, clinical manifestations had completely despeared in 31(91.2%)patients in non-severe group, and 18(85.7%) patients in severe group (p = 0.85). Both groups had a satisfied chest CT imaging recovery, which includes 22(64.7%) patients in non-severe group and 12(57.1%) patients in severe group recovered at least 50% of the whole leisions in the first week, and 28(82.4%) and 16(76.2%) recovered at least 75% in the second week, respectively. There were no significant differences in SARS-CoV-2 nucleic acid negativity (p = 0.92). There were also no significant differences in the levels of SARS-CoV-2-IgM and IgG antibody production between the two groups (p = 0.13, 0.62). There were 45 cases were discharged from the hospital, and no patients died at the time of this clinical analysis. CONCLUSIONS: Risk-adapted treatment strategy was associated with significant clinical manifestations alleviation and clinical imaging recovery. In severe COVID-19 patients, early and short-term use of low-dose methylprednisolone was beneficial and did not delay SARS-CoV-2 nucleic acid clearance and influence IgG antibody production.

negative: How are adversities during COVID-19 affecting mental health? Differential associations for worries and experiences and implications for policy Background: There are concerns that COVID-19 is having adverse effects on mental health. But it remains unclear whether this is being caused by worries over potential adversities due to the pandemic, or the toll of experiencing adverse events. Aims: To explore the time-varying longitudinal relationship between (i) worries about adversity, and (ii) experience of adversity, and both anxiety and depression and test the moderating role of socio-economic position. Methods: Data from 35,784 UK adults in the UCL COVID -19 Social Study (a panel study collecting data weekly during the Covid-19 pandemic) were analysed from 01/04/2020-28/04/2020. The sample was well-stratified and weighted to population proportions of gender, age, ethnicity, education and geographical location. Fixed effects regression was used to explore within-person variation over time. Results: Cumulative number of worries and experience of adversities were both related to higher levels of anxiety and depression. Number of worries were associated more with anxiety than depression, but number of experiences were equally related to anxiety and depression. Individuals of lower socio-economic position were more negatively affected psychologically by adverse experiences. Conclusions: Measures over the first few weeks of lockdown in the UK appear to have been insufficient at reassuring people given we are still seeing clear associations with poor mental health both for cumulative worries and also for a range of specific worries relating to finance, access to essentials, personal safety and COVID-19. Interventions are required that both seek to prevent adverse events (e.g. redundancies) and that reassure individuals and support adaptive coping strategies.

negative: Acute kidney injury in hospitalized children: consequences and outcomes Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events.

negative: Psychosocial impact of COVID-19 BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as “coronaphobia”, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Psychology”, “Psychosocial”, “Psychitry”, “marginalized”, “telemedicine”, “mental health”, “quarantine”, “infodemic”, “social media” and” “internet”. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an “infodemic” spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.

negative: PTSD as the second tsunami of the SARS-Cov-2 pandemic Since the first cases, the coronavirus disease (COVID-19) rapidly spread around the world, with hundred-thousand cases and thousands of deaths. Post-traumatic stress disorder (PTSD) is a common consequence of major disasters. Exceptional epidemic situations also promoted PTSD in the past. Considering that humanity is undergoing the most severe pandemic since Spanish Influenza, the actual pandemic of COVID-19 is very likely to promote PTSD. Moreover, COVID-19 was renamed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). With a poor understanding of viruses and spreading mechanisms, the evocation of SARS is generating a great anxiety contributing to promote PTSD. Quarantine of infected patients evolved to quarantine of 'infected' towns or popular districts, and then of entire countries. In the families of cases, the brutal death of family members involved a spread of fear and a loss of certainty, promoting PTSD. In the context of disaster medicine with a lack of human and technical resources, healthcare workers could also develop acute stress disorders, potentially degenerating into chronic PTSD. Globally, WHO estimates 30-50% of the population affected by a disaster suffered from diverse psychological distress. PTSD individuals are more at-risk of suicidal ideation, suicide attempt, and deaths by suicide - considering that healthcare workers are already at-risk occupations. We draw attention towards PTSD as a secondary effect of the SARS-Cov-2 pandemic, both for general population, patients, and healthcare workers. Healthcare policies need to take into account preventive strategy of PTSD, and the related risk of suicide, in forthcoming months.

negative: Estimating Workforce-Related Economic Impact of a Pandemic on the Commonwealth of Virginia A pandemic outbreak is one of the major planning scenarios considered by emergency-preparedness policymakers. The consequences of a pandemic can significantly affect and disrupt a large spectrum of workforce sectors in today's society. This paper, motivated by the impact of a pandemic, extends the formulation of the dynamic inoperability input–output model (DIIM) to account for economic perturbations resulting from such an event, which creates a time-varying and probabilistic inoperability to the workforce. A pandemic is a unique disaster, because the majority of its direct impacts are workforce related and it does not create significant direct impact to infrastructure. In light of this factor, this paper first develops a method of translating unavailable workforce into a measure of economic-sector inoperability. While previous formulations of the DIIM only allowed for the specification of an initial perturbation, this paper incorporates the fact that a pandemic can cause direct effects to the workforce over the recovery period. Given the uncertainty associated with the impact of a pandemic, this paper develops a simulation framework to account for the possible variations in realizations of the pandemic. The enhancements to the DIIM formulation are incorporated into a MatLab program and then applied to a case study to simulate a pandemic scenario in the Commonwealth of Virginia.

negative: Psychological intervention with sufferers from severe acute respiratory syndrome (SARS): lessons learnt from empirical findings In 2003, severe acute respiratory syndrome (SARS) severely hit Hong Kong. We conducted a series of five studies examining the psychological impacts of SARS on the sufferers. Results showed that (1) various psychiatric complications emerged in the acute treatment phase; (2) certain types of behavioral and verbal responses of health‐care workers (HCWs) were able to ameliorate the psychological distress of the sufferers in the acute phase; (3) the short‐term adjustment outcomes of the sufferers were unsatisfactory; (4) ‘being an HCW’ and ‘having a family member killed by SARS’ were risk factors predisposing individuals to the development of high distress after discharge; and (5) after controlling for the effects of demographic and risk factors psychosocial factors such as social support, negative appraisal (or perceived impact), positive appraisal (or post‐traumatic growth) and self‐efficacy could account for substantial variances of differential outcomes including symptoms of anxiety and depression, quality of life and perceived health of the sufferers. This practitioner report aims to summarize the key findings, which have significant clinical implications in the provision of psychological intervention to the sufferers of SARS or other comparable infectious diseases. Copyright © 2004 John Wiley & Sons, Ltd.

negative: Complicated Grief: What to Expect After the Coronavirus Pandemic The COVID-19 pandemic is one of the worst public health crises in a century, with an expected amount of deaths of several million worldwide and an even bigger number of bereaved people left behind. Although the consequences of this crisis are still unknown, a significant number of bereaved people will arguably develop Complicated Grief (CG) in the aftermath of this emergency. If the current pandemic is unprecedented, the grief following the coronavirus outbreak is likely to share features with grief related to natural disasters and after Intensive Care Unit (ICU) treatment. The aim of this paper is to review the most prominent literature on CG after natural disasters, as well as after diseases requiring ICU treatment. This body of evidence may be useful for helping bereaved people during the acute phase of the COVID-19 pandemic and for drawing clinical attention to people at risk for CG.

negative: PTSD as the second tsunami of the SARS-Cov-2 pandemic Since the first cases, the coronavirus disease (COVID-19) rapidly spread around the world, with hundred−thousand cases and thousands of deaths. Post-traumatic stress disorder (PTSD) is a common consequence of major disasters. Exceptional epidemic situations also promoted PTSD in the past. Considering that humanity is undergoing the most severe pandemic since Spanish Influenza, the actual pandemic of COVID-19 is very likely to promote PTSD. Moreover, COVID-19 was renamed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). With a poor understanding of viruses and spreading mechanisms, the evocation of SARS is generating a great anxiety contributing to promote PTSD. Quarantine of infected patients evolved to quarantine of ‘infected’ towns or popular districts, and then of entire countries. In the families of cases, the brutal death of family members involved a spread of fear and a loss of certainty, promoting PTSD. In the context of disaster medicine with a lack of human and technical resources, healthcare workers could also develop acute stress disorders, potentially degenerating into chronic PTSD. Globally, WHO estimates 30–50% of the population affected by a disaster suffered from diverse psychological distress. PTSD individuals are more at-risk of suicidal ideation, suicide attempt, and deaths by suicide – considering that healthcare workers are already at-risk occupations. We draw attention towards PTSD as a secondary effect of the SARS-Cov-2 pandemic, both for general population, patients, and healthcare workers. Healthcare policies need to take into account preventive strategy of PTSD, and the related risk of suicide, in forthcoming months.

negative: In silico studies on therapeutic agents for COVID-19: Drug repurposing approach AIMS: The severe acute respiratory syndrome coronavirus 2, better known as COVID-19 has become the current health concern to the entire world. Initially appeared in Wuhan, China around December 2019, it had spread to almost 187 countries due to its high contagious nature. Precautionary measures remain the sole obliging tactic to cease the person to person transmissions till any effective method of treatment or vaccine is developed. Amidst the pandemic, research and development of new molecule is labour-intensive and tedious process. Drug repurposing is the concept of identifying therapeutically potent molecule from the library of pre-existing molecules. MATERIALS AND METHODS: In the present study, 61 molecules that are already being used in clinics or under clinical scrutiny as antiviral agents are surveyed via docking study. Docking study was performed using Maestro interface (Schrödinger Suite, LLC, NY). KEY FINDINGS: Out of these 61 molecules, 37 molecules were found to interact with >2 protein structures of COVID-19. The docking results indicate that amongst the reported molecules, HIV protease inhibitors and RNA-dependent RNA polymerase inhibitors showed promising features of binding to COVID-19 enzyme. Along with these, Methisazone an inhibitor of protein synthesis, CGP42112A an angiotensin AT2 receptor agonist and ABT450 an inhibitor of the non-structural protein 3-4A might become convenient treatment option as well against COVID-19. SIGNIFICANCE: The drug repurposing approach provide an insight about the therapeutics that might be helpful in treating corona virus disease.

negative: [CoViD-19 and stress in the pandemic: "sanity is not statistical"]. CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including Italy. The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.

negative: A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 PURPOSE: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19. METHODS: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19. RESULTS: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro. CONCLUSIONS: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed.

negative: Will COVID-19 fiscal recovery packages accelerate or retard progress on climate change? The COVID-19 crisis is likely to have dramatic consequences for progress on climate change. Imminent fiscal recovery packages could entrench or partly displace the current fossil-fuel-intensive economic system. Here, we survey 231 central bank officials, finance ministry officials, and other economic experts from G20 countries on the relative performance of 25 major fiscal recovery archetypes across four dimensions: speed of implementation, economic multiplier, climate impact potential, and overall desirability. We identify five policies with high potential on both economic multiplier and climate impact metrics: clean physical infrastructure, building efficiency retrofits, investment in education and training, natural capital investment, and clean R&D. In lower- and middle-income countries (LMICs) rural support spending is of particular value while clean R&D is less important. These recommendations are contextualised through analysis of the short-run impacts of COVID-19 on greenhouse gas curtailment and plausible medium-run shifts in the habits and behaviours of humans and institutions.

negative: The Restructuring of Structural Heart Disease Practice During The Covid-19 Pandemic Abstract Patients with structural heart disease (SHD) are at increased risk of adverse outcomes from the coronavirus disease 19 (COVID-19) due to advanced age and comorbidity. In the midst of a global pandemic of a novel infectious disease, reality-based considerations comprise an important starting point for formulating clinical management pathways. The aim of these “crisis-driven” recommendations is (1) to ensure appropriate and timely treatment of SHD patients, (2) to minimize the risk of COVID-19 exposure to patients and healthcare workers, and (3) to limit resource utilization under conditions of constraint. While the degree of disruption to usual practice will vary across the United States and elsewhere, we hope that early experiences from a Heart Team operating in the current global epicenter of COVID-19 may prove useful for others adapting their practice in advance of local surges of COVID-19.

negative: SARS CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus. Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.

negative: Clinical Decision Support Tool and Rapid Point-of-Care Platform for Determining Disease Severity in Patients with COVID-19 SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40–83) and 9 (6–17), respectively, and area under the curve of 0.94 (95% CI 0.89–0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.

negative: Fire, disease and fear: Effects of the media coverage of 2019-2020 Australian bushfires and novel coronavirus 2019 on population mental health.

negative: Survival of Severe Acute Respiratory Syndrome Coronavirus Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.

negative: The CoRisk-Index: A data-mining approach to identify industry-specific risk assessments related to COVID-19 in real-time While the coronavirus spreads, governments are attempting to reduce contagion rates at the expense of negative economic effects. Market expectations plummeted, foreshadowing the risk of a global economic crisis and mass unemployment. Governments provide huge financial aid programmes to mitigate the economic shocks. To achieve higher effectiveness with such policy measures, it is key to identify the industries that are most in need of support. In this study, we introduce a data-mining approach to measure industry-specific risks related to COVID-19. We examine company risk reports filed to the U.S. Securities and Exchange Commission (SEC). This alternative data set can complement more traditional economic indicators in times of the fast-evolving crisis as it allows for a real-time analysis of risk assessments. Preliminary findings suggest that the companies' awareness towards corona-related business risks is ahead of the overall stock market developments. Our approach allows to distinguish the industries by their risk awareness towards COVID-19. Based on natural language processing, we identify corona-related risk topics and their perceived relevance for different industries. The preliminary findings are summarised as an up-to-date online index. The CoRisk-Index tracks the industry-specific risk assessments related to the crisis, as it spreads through the economy. The tracking tool is updated weekly. It could provide relevant empirical data to inform models on the economic effects of the crisis. Such complementary empirical information could ultimately help policymakers to effectively target financial support in order to mitigate the economic shocks of the crisis.

negative: Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study Background: COVID-19 is an emerging disease caused by the SARS-CoV-2 virus; no specific medication has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19. Methods: This single-center, retrospective, and observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Demographic information, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and eight patients with mild and severe symptoms, respectively. Findings: All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all eight severe-group patients (median treatment: 17.5 days; four received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all eight in the severe group (median treatment: 9 days; two received linezolid). Moreover, seven patients (12.72%) were treated with glucocorticoids and nine (16.36%) with immunomodulators. Interpretation: Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary.

negative: A follow-up study of children infected with SARS-CoV-2 from Western China Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in Western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD=7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

negative: Single particle assay of coronavirus membrane fusion with proteinaceous receptor-embedded supported bilayers Abstract Total internal reflection microscopy combined with microfluidics and supported bilayers is a powerful, single particle tracking (SPT) platform for host-pathogen membrane fusion studies. But one major inadequacy of this platform has been capturing the complexity of the cell membrane, including membrane proteins. Because of this, viruses requiring proteinaceous receptors, or other unknown cellular co-factors, have been precluded from study. Here we describe a general method to integrate proteinaceous receptors and cellular components into supported bilayers for SPT fusion studies. This method is general to any enveloped virus-host cell pair, but demonstrated here for feline coronavirus (FCoV). Supported bilayers are formed from mammalian cell membrane vesicles that express feline aminopeptidase N (the viral receptor) using a cell blebbing technique. SPT is then used to identify fusion intermediates and measure membrane fusion kinetics for FCoV. Overall, the fusion results recapitulate what is observed in vivo, that coronavirus entry requires binding to specific receptors, a low-pH environment, and that membrane fusion is receptor- and protease-dependent. But this method also provides quantitative kinetic rate parameters for intermediate steps in the coronavirus fusion pathway, which to our knowledge have not been obtained before. Moreover, the platform offers versatile, precise control over the sequence of triggers for fusion; these triggers may define the fusion pathway, tissue tropism, and pathogenicity of coronaviruses. Systematically varying these triggers in this platform provides a new route to study how viruses rapidly adapt to other hosts, and to identify factors that led to the emergence of zoonotic viruses, such as human SARS-CoV and the newly emerging human MERS-CoV.

negative: Cross-Country Comparison of Case Fatality Rates of COVID-19/SARS-COV-2 OBJECTIVES: Case fatality rates (CFR) and recovery rates are important readouts during epidemics and pandemics. In this article, an international analysis was performed on the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data were retrieved from accurate databases according to the user’s guide of data sources for patient registries, CFR and recovery rates were calculated for each country. A comparison of CFR between countries with total cases ≥ 1,000 was observed for 12(th) and 23(rd) March. RESULTS: Italy’s CFR was the highest of all countries studied for both time points (12(th) March, 6.22% versus 23(rd) March, 9.26%). The data showed that even though Italy was the only European country reported on 12(rd) March, Spain and France had the highest CFR of 6.16 and 4.21%, respectively, on 23(rd) March, which was strikingly higher than the overall CFR of 3.61%. CONCLUSION: Obtaining detailed and accurate medical history from COVID-19 patients, and analyzing CFR alongside the recovery rate, may enable the identification of the highest risk areas so that efficient medical care may be provided. This may lead to the development of point-of-care tools to help clinicians in stratifying patients based on possible requirements in the level of care, to increase the probabilities of survival from COVID-19 disease.

negative: COVID-19 or Lung Cancer: what should we treat?

negative: Global Infodemiology of COVID-19: Focus on Google web searches and Instagram hashtags Background: Several studies have been conducted using 'infodemiological' methods in COVID-19 research, but studies focusing to examine the extent of infodemic monikers (misinformation) on the internet is very limited. Aim: We aimed to investigate the internet search behavior related to COVID-19 and the extent of infodemic monikers circulating in Google and Instagram during the pandemic period in the world. Methods: Using Google Trends and Instagram hashtags (#), we explored the internet search activities and behaviors related to COVID-19 pandemic all over the world from February 20, 2020, to May 06, 2020. Briefly, we investigated the names used to identify the virus, health and risk perception, life during the lockdown, and also information related to the adoption of infodemic monikers related to COVID-19. We computed the average peak volume (APC) with a 95% confidence interval (CI) during the study period. Results: The top five COVID-19 related terms used in Google searches were "coronavirus", "corona", "COVID", "virus", "corona virus", and "COVID-19". Countries with a higher number of COVID-19 cases have greater Google searches queries related to COVID-19. "coronavirus ozone", "coronavirus laboratory", "coronavirus 5G", "coronavirus conspiracy" and "coronavirus bill gates" are widely circulated infodemic monikers on the internet. Searches related to 'tips and cures' to COVID-19 spiked when the US president suggested an unproven drug as a 'miracle cure' and suggested injecting disinfectant to treat COVID-19. Around two-thirds (66.1%) of the Instagram users use "COVID-19", and "coronavirus" hashtags to disperse the information related to COVID-19. Conclusion: Globally, there is a growing interest in COVID-19 and a large number of infodemic monikers are circulating on the internet. Therefore, mass media regulators and health organizers should be vigilant to diminish the infodemic monikers dispersing on the internet and also should take serious actions against those spreading misinformation in social media.

negative: Adverse effects of isolation in hospitalised patients: a systematic review Summary The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

negative: Clinical characteristics and reasons of different duration from onset to release from quarantine for patients with COVID-19 Outside Hubei province, China. Objective: To find out more characteristics and rules of COVID-19 by analyzing the clinical course of COVID-19 patients in a region outside Hubei province. Methods: 37 cases diagnosed adult COVID-19 cases of general characteristics, history of epidemiology, chronic underlying diseases,clinical symptoms and complications, chest CT, biochemical monitoring, severity assessment, treatment and outcome were retrospectively analyzed, and according to the duration from onset to release from quarantine were divided into 20-day group and > 20-day group, compare the similarities and differences between the two groups. Results: Among the 37 patients, 5 were mild, 30 were moderate, 1 was severe and 1 was critical. All the patients were released from quarantine without death. The average duration from onset to release from quarantine was 20.2±6.6 days, The average length of stay from onset to hospitalization was 4.1±3.7 days, and hospitalization duration average 16.1± 6.2 days. The average age was 44.3±1.67 years. 78.4% of cases were caused by exposure to a confirmed patient or the workplace of a confirmed patient. The main symptoms were cough (67.6%), fever( 62.2%), shortness of breath (32.4%), fatigue (24.3%), sore throat (21.6%,) vomiting or diarrhea (21.6%). The white blood cell count was decreased in 27.0% of the patients, and the lymphocyte count was decreased in 62.2% of the patients, of which 43.5% patients were <0.6 × 109/L. On admission, 86.5% of patients with chest CT showed pneumonia, including some asymptomatic patients. 68.8% of patients showed bilateral infiltration. In the > 20-day group, the average age was 49.9±1.38 years old, and the duration from onset to hospitalization was 5.5±3.9 days. Compared with the ≤20-day group, the age was older and and duration was longer, P < 0.05. All the 7 asymptomatic patients were ≤20-day group. When 37 patients were released from quarantine, the white blood cell count of 16.2% patients was <4.0 × 109/L, and the lymphocyte count of 59.5% patients was <1.1×109/L, and the absolute count of white blood cells and lymphocytes was 5.02 ± 1.34×109/L and 1.03± 0.34×109/L respectively , compared with those on admission, P >0.05. Conclusion: The majority of COVID-19 cases in the study area were mild and moderate, with good clinical outcomes. There were some special characteristics in the clinical process. The reasons of duration from onset to release from quarantine were complex. There was no significant change in the number of granulocytes at the time of release from quarantine compared to the time of admission.

negative: Applying Telehealth Technologies and Strategies to Provide Acute Care Consultation and Treatment of Patients With Confirmed or Possible COVID-19 BACKGROUND AND PURPOSE: The COVID-19 pandemic continues to grow, with 19% of total confirmed patients classified as severe or critical experiencing complications such as dyspnea, hypoxia, acute respiratory distress syndrome, or multiorgan failure. These complications require rehabilitative care. Considering the contagious nature of COVID-19 and the necessity to decrease the volume of health care professionals entering confirmed COVID-19 patient rooms and becoming a potential disease vector, can audiovisual technologies employed by telehealth and telerehabilitation help? CASE DESCRIPTION: This case discusses the Baylor Scott and White Institute for Rehab (BSWIR) Physical Medicine and Rehabilitation (PMR) department COVID-19 acute care therapy team's creation of a telehealth strategy to provide early rehabilitative intervention without increasing the odds of disease transmission. OUTCOMES: The COVID-19 therapy team created a simple process for identifying and triaging care for patients with possible or confirmed COVID-19. These patients were evaluated and treated by the dedicated team using telehealth strategies. A structured risk-benefit analysis was used to determine when in-room care was indicated. DISCUSSION: Acute care physical therapy, occupational therapy, and speech-language pathology telehealth strategies can add value by mitigating COVID-19–related harm and influencing recovery, while not unnecessarily becoming additional disease vectors consuming personal protective equipment. COVID-19 is not only an aggressive respiratory illness similar to acute respiratory distress syndrome but also highly contagious and a risk for health care providers. Telehealth strategies allow therapists to intervene early, opening the possibility to maximize recovery and prevent harm or decompensation. Telehealth strategies can be more prevention-focused while the patient is experiencing relatively good health with goals to maximize strength and endurance before the disease process evolves to critical illness. As COVID-19 progresses, therapy can help mitigate potential complications associated with prolonged intensive care unit stay and ventilator management.

negative: The Progression of Computed Tomographic (CT) Images in Patients with Coronavirus Disease (COVID-19) Pneumonia The CT progression of COVID-19 pneumonia • Of the 49 patients, 89.8% (44/49) patients had a typical transition from early stage to advanced stage, and then from advanced stage to dissipating stage. • With the evidence of fibrosis for progression of CT results, 42.9% (21/49) patients developed fibrosis whereas 57.1% (28/49) patients demonstrated no definite fibrosis. • Patients with fibrosis in follow CT were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), and higher rate of ICU admission (19.0% [4/21] vs. 3.6% [1/28]) than that of those without fibrosis.

negative: The closer to the Europe Union headquarters, the higher risk of COVID-19? Cautions regarding ecological studies of COVID-19 Several ecological studies of the coronavirus disease 2019 (COVID-19) have reported correlations between group-level aggregated exposures and COVID-19 outcomes. While some studies might be helpful in generating new hypotheses related to COVID-19, results of such type of studies should be interpreted with cautions. To illustrate how ecological studies and results could be biased, we conducted an ecological study of COVID-19 outcomes and the distance to Brussels using European country-level data. We found that, the distance was negatively correlated with COVID-19 outcomes; every 100 km away from Brussels was associated with approximately 6% to 17% reductions (all P<0.01) in COVID-19 cases and deaths in Europe. Without cautions, such results could be interpreted as the closer to the Europe Union headquarters, the higher risk of COVID-19 in Europe. However, these results are more likely to reflect the differences in the timing of and the responding to the outbreak, etc. between European countries, rather than the 'effect' of the distance to Brussels itself. Associations observed at the group level have limitations to reflect individual-level associations - the so-called ecological fallacy. Given the public concern over COVID-19, ecological studies should be conducted and interpreted with great cautions, in case the results would be mistakenly understood.

negative: Sampling methods for recovery of human enteric viruses from environmental surfaces Abstract Acute gastroenteritis causes the second highest infectious disease burden worldwide. Human enteric viruses have been identified as leading causative agents of acute gastroenteritis as well as foodborne illnesses in the U.S. and are generally transmitted by fecal-oral contamination. There is growing evidence of transmission occurring via contaminated fomite including food contact surfaces. Additionally, human enteric viruses have been shown to remain infectious on fomites over prolonged periods of time. To better understand viral persistence, there is a need for more studies to investigate this phenomenon. Therefore, optimization of surface sampling methods is essential to aid in understanding environmental contamination to ensure proper preventative measures are being applied. In general, surface sampling studies are limited and highly variable among recovery efficiencies and research parameters used (e.g., virus type/density, surface type, elution buffers, tools). This review aims to discuss the various factors impacting surface sampling of viruses from fomites and to explore how researchers could move towards a more sensitive and standard sampling method.

negative: A novel COVID-19 and its effects on cardiovascular disease

negative: Pandémie COVID-19 : impact sur le systeme cardiovasculaire. Données disponibles au 1er avril 2020 Résumé Le syndrome respiratoire aigu sévère coronavirus 2 (SARS-CoV-2) infecte les cellules hôtes par les récepteurs de l’angiotensine, conduisant à une pneumonie liée au COVID-19. À un niveau cardiaque, le virus a un double impact ; en effet, l’infection sera plus grave si l’hôte possède des comorbidités cardiovasculaires, et le virus peut causer des lésions cardiovasculaires pouvant engager le pronostic vital. Les thérapeutiques associées au COVID-19 peuvent avoir des effets indésirables cardiovasculaires. Une attention particulière doit être accordée à la protection cardiovasculaire pendant l’infection au COVID-19. Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.

negative: Cardiovascular complications in COVID-19 BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

negative: COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.

negative: Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes

negative: COVID-19Base: A knowledgebase to explore biomedical entities related to COVID-19 We are presenting COVID-19Base, a knowledgebase highlighting the biomedical entities related to COVID-19 disease based on literature mining. To develop COVID-19Base, we mine the information from publicly available scientific literature and related public resources. We considered seven topic-specific dictionaries, including human genes, human miRNAs, human lncRNAs, diseases, Protein Databank, drugs, and drug side effects, are integrated to mine all scientific evidence related to COVID-19. We have employed an automated literature mining and labeling system through a novel approach to measure the effectiveness of drugs against diseases based on natural language processing, sentiment analysis, and deep learning. To the best of our knowledge, this is the first knowledgebase dedicated to COVID-19, which integrates such large variety of related biomedical entities through literature mining. Proper investigation of the mined biomedical entities along with the identified interactions among those, reported in COVID-19Base, would help the research community to discover possible ways for the therapeutic treatment of COVID-19.

negative: Epidemiology and Transmission of COVID-19 in Shenzhen China: Analysis of 391 cases and 1,286 of their close contacts Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Shenzhen and elsewhere in China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control. Methods The Shenzhen CDC identified 391 SARS-CoV-2 cases from January 14 to February 12, 2020 and 1286 close contacts. We compare cases identified through symptomatic surveillance and contact tracing, and estimate the time from symptom onset to confirmation, isolation, and hospitalization. We estimate metrics of disease transmission and analyze factors influencing transmission risk. Findings Cases were older than the general population (mean age 45) and balanced between males (187) and females (204). Ninety-one percent had mild or moderate clinical severity at initial assessment. Three have died, 225 have recovered (median time to recovery is 21 days). Cases were isolated on average 4.6 days after developing symptoms; contact tracing reduced this by 1.9 days. Household contacts and those travelling with a case where at higher risk of infection (ORs 6 and 7) than other close contacts. The household secondary attack rate was 15%, and children were as likely to be infected as adults. The observed reproductive number was 0.4, with a mean serial interval of 6.3 days. Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into SARS-CoV-2 epidemiology. This work shows that heightened surveillance and isolation, particularly contact tracing, reduces the time cases are infectious in the community, thereby reducing R. Its overall impact, however, is uncertain and highly dependent on the number of asymptomatic cases. We further show that children are at similar risk of infection as the general population, though less likely to have severe symptoms; hence should be considered in analyses of transmission and control.

negative: Incidence of Adverse Drug Reactions in COVID-19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System To evaluate the incidence, type, and risk factors associated with adverse drug reactions (ADRs) among patients with coronavirus disease 2019 (COVID-19) by Hospital Pharmacovigilance System (CHPS). A retrospective analysis was performed on 217 patients with COVID-19 admitted to the First Hospital of Changsha in China, from January 17, 2020, to February 29, 2020. The active monitoring model in CHPS was used to detect ADR signals of the hospital information system. The risk factors for the ADRs were classified using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system. Univariate and multivariate logistic regressions were carried out to analyze the risk factors of ADRs. Our results showed that the prevalence of ADRs was 37.8% in the patients, which was predominated by drug-induced gastrointestinal disorders and liver system disorders (23.0% vs. 13.8%). The ADR could be explained by the use of lopinavir/ ritonavir and umifenovir by 63.8% and 18.1%, respectively. There were 96.8% of ADRs that occurred within 14 days of hospitalization. Multivariable analysis showed that length of stay (odds ratio (OR): 2.02; 95% confidence interval (CI) 1.03-3.96; P = 0.04), number of drugs used in the hospital (OR: 3.17; 95% CI 1.60-6.27; P = 0.001) and underlying basic diseases (OR: 2.07; 95% CI 1.02-4.23; P = 0.04) were independent risk factor for ADRs in the patients. Together, the incidence of ADRs was significantly high during the treatment period. Moreover, the active monitoring of the CHPS system reflected ADRs during COVID-19 treatment in the real world, which provided reference for safe medication in the clinic.

negative: Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study At the end of December 2019, a novel strain of coronavirus, given the name of 2019-nCoV, emerged for exhibiting symptoms of severe acute respiratory syndrome. The virus is spreading rapidly in China and around the globe, affecting thousands of people leading to a pandemic. To control the mortality rate associated with the 2019-nCoV, prompt steps are needed. Until now there is no effective treatment or drug present to control its life-threatening effects in the humans. The scientist is struggling to find new inhibitors of this deadly virus. In this study, to identify the effective inhibitor candidates against the main protease (Mpro) of 2019-nCoV, computational approaches were adopted. Phytochemicals having immense medicinal properties as ligands were docked against the Mpro of 2019-nCoV to study their binding properties. ADMET and DFT analyses were also further carried out to analyze the potential of these phytochemicals as an effective inhibitor against Mpro of 2019-nCoV.

negative: Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.

negative: Assessment of Health Information About COVID-19 Prevention on the Internet: Infodemiological Study BACKGROUND: The internet is a large source of health information and has the capacity to influence its users. However, the information found on the internet often lacks scientific rigor, as anyone may upload content. This factor is a cause of great concern to scientific societies, governments, and users. OBJECTIVE: The objective of our study was to investigate the information about the prevention of coronavirus disease 2019 (COVID-19) on the internet. METHODS: On February 29, 2020, we performed a Google search with the terms "Prevention coronavirus," "Prevention COVID-19," "Prevención coronavirus," and "Prevención COVID-19". A univariate analysis was performed to study the association between the type of authorship, country of publication, and recommendations to avoid COVID-19 according to the World Health Organization (WHO). RESULTS: In total, 80 weblinks were reviewed. Most of them were produced in the United States and Spain (n=58, 73%) by digital media sources and official public health organizations (n=60, 75%). The most mentioned WHO preventive measure was "wash your hands frequently" (n=65, 81%). A less frequent recommendation was to "stay home if you feel unwell" (n=26, 33%). The analysis by type of author (official public health organizations versus digital media) revealed significant differences regarding the recommendation to wear a mask when you are healthy only if caring for a person with suspected COVID-19 (odds ratio [OR] 4.39). According to the country of publication (Spain versus the United States), significant differences were detected regarding some recommendations such as "wash your hands frequently" (OR 9.82), "cover your mouth and nose with your bent elbow or tissue when you cough or sneeze" (OR 4.59), or "stay home if you feel unwell" (OR 0.31). CONCLUSIONS: It is necessary to urge and promote the use of the websites of official public health organizations when seeking information on COVID-19 preventive measures on the internet. In this way, users will be able to obtain high-quality information more frequently, and such websites may improve their accessibility and positioning, given that search engines justify the positioning of links obtained in a search based on the frequency of access to them.

negative: Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up Summary Objective To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. Methods Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. Results 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3–8) vs. 28 (26–29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). Conclusions High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.

negative: Taking the Longer View of COVID‐19 What are the prospects for dealing with COVID‐19 more effectively in the future? This editorial addresses the question from the perspective of long‐term control of coronavirus infection.

negative: Effects of city-size heterogeneity on epidemic spreading in a metapopulation: A reaction-diffusion approach We review and introduce a generalized reaction-diffusion approach to epidemic spreading in a metapopulation modeled as a complex network. The metapopulation consists of susceptible and infected individuals that are grouped in subpopulations symbolising cities and villages that are coupled by human travel in a transportation network. By analytic methods and numerical simulations we calculate the fraction of infected people in the metaopoluation in the long time limit, as well as the relevant parameters characterising the epidemic threshold that separates an epidemic from a non-epidemic phase. Within this model, we investigate the effect of a heterogeneous network topology and a heterogeneous subpopulation size distribution. Such a system is suited for epidemic modeling where small villages and big cities exist simultaneously in the metapopulation. We find that the heterogeneous conditions cause the epidemic threshold to be a non-trivial function of the reaction rates (local parameters), the network's topology (global parameters) and the cross-over population size that separates"village dynamics"from"city dynamics".

negative: Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 BACKGROUND: There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. OBJECTIVE: Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19. METHODS: IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. RESULTS: The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. CONCLUSIONS: The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.

negative: Abstracts from the 11th International Congress of Behavioral Medicine

negative: Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.

negative: Neurologic aspects of covid-19: a concise review In addition to the conventional respiratory symptoms, patients with COVID-19 can exhibit neurological complications In this concise review, we aim to report the most frequent neurologic manifestations related to Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) infection SARS-CoV2 can reach the central nervous system from the bloodstream or olfactory pathway by binding ACE-2 receptor and the spike protein protease TMPRSS2 Headache is reported in more than 10% of affected patients and loss of smell and taste disturbance are reported in a slightly smaller percentage of cases Acute cerebrovascular events are diagnosed in less than 3% of COVID-19 patients, but those with more severe manifestations have cerebrovascular events in more than 6% of the cases, as reported by two retrospective studies from Italy and China Moreover, five cases of large-vessel stroke have been described in low-symptomatic COVID-19 patients aging less than 50 years suggesting that SARS-CoV2 can be associated with an increase of the risk of stroke in relatively young people Peripheral nerve diseases can be observed after an apparently uneventful SARS-CoV2 Based on a literature review, nine patients experienced Guillain-Barre syndrome (GBS) and 6 of these needed mechanical ventilation Two more cases have been described with Miller-Fisher syndrome or polyneuritis cranialis, both had rapidly resolving symptoms In conclusion, nervous system symptoms can be observed during SARS-CoV2 infection of which headache and smell and taste disturbance are the main symptoms reported Cerebrovascular complications can complicate the course of COVID-19 in apparently low-risk patients GBS is a life-threatening manifestation of COVID-19

negative: Prise en charge des infections des voies respiratoires basses de l'immunocompétent. Partie concernant les définitions, l'épidémiologie et les éléments du diagnostic Résumé Les infections respiratoires basses sont une des principales cause de mortalité dans le monde et les pneumopathies représentent en France la première cause de décès d'origine infectieuse. Trois entités nosologiques distinctes sont habituellement isolées en fonction de la localisation infectieuse : la bronchite aiguë, la pneumopathie et la bronchopneumopathie (atteignant les bronches et le parenchyme pulmonaire). En cas d'infections de l'arbre bronchique dans le cadre d'une bronchopathie chronique on parle de décompensation infectieuse de la maladie bronchique. Les deux principales difficultés diagnostiques de ces infections sont de déterminer la présence d'une participation alvéolaire au processus infectieux et de définir l'agent (ou les agents) pathogènes. Ces deux éléments vont conditionner la prise en charge thérapeutique. En dehors de l'examen physique, indispensable dans ce contexte, seule la radiographie thoracique pourra, en cas de persistance d'un doute, permettre de confirmer la présence d'une participation alvéolaire. Le diagnostic microbiologique pose la question de sa nécessité systématique et celui de sa valeur. Il n'est pas indispensable de réaliser un diagnostic microbiologique de certitude dans tous les cas. La décision de documentation doit répondre à deux impératifs : faisabilité et valeur diagnostique. La valeur d'un prélèvement dépend de son aptitude à mettre en évidence l'agent pathogène et dans certains cas de la possibilité d'en déterminer le profil de sensibilité (qui reste une indication majeure à la réalisation de ces prélèvements). Abstract Particular attention is given to lower respiratory tract infections because of their frequency and potential severity. These infections represent a major cause of death worldwide and pneumonia remains the first cause of death from infectious origin in France. Three nosological entities are usually described according to the anatomic localization of the infectious process: acute bronchitis, pneumonia, and bronchopneumonia (if the infection involves the bronchial tree and the lung parenchyma). If bronchial infection occurs within the context of a chronic respiratory tract disease, it is called acute decompensation of chronic lung disease (usually chronic obstructive pulmonary disease). The major diagnostic difficulties are to be able to confirm alveolar implication in the infectious process and to determine the pathogenic agent(s) responsible for the clinical pattern. This information is essential for subsequent care depends. Apart from clinical examination, essential in this context, only chest-X-rays can be of any help to confirm alveolar involvement in the disease process. On the contrary, the interest of systematic microbiological confirmation and its value according to various techniques and swab conditions may be questioned for the clinical diagnosis. Microbiological confirmation does not seem essential in every case. The feasibility and relevance of microbiological techniques must be determined before any decision is taken on documentation. The microbiological documentation value depends on its yield and sensitivity profile in identifying the pathogen.

negative: Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

negative: Risks Posed to Corneal Transplant Recipients by COVID-19-Affected Donors The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant human disease, COVID-19, will likely have a significant impact on the corneal tissue donor pool. Current recommendations from the United States and global eye bank associations call for the outright avoidance of tissues from donors recently infected with or exposed to COVID-19. This conservative recommendation is currently appropriate given the reported ocular sequelae, tear film viral detectability, and transmissibility of COVID-19. However, the rapidly increasing global prevalence and mortality of COVID-19 threatens the tenability of current tissue exclusion guidelines, and may necessitate their relaxation in the near future.

negative: Asymptomatic SARS‐CoV‐2 infected case with viral detection positive in stool but negative in nasopharyngeal samples lasts for 42 days Coronavirus disease 2019 (COVID‐19), caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread rapidly around the world. Currently, the identification of this disease is mainly conducted by using nasopharyngeal swabs([1]), but the presence of SARS‐CoV‐2 RNA in feces of COVID‐19 patients indicates the possibility of transmission via fecal‐oral route([2‐4]). This article is protected by copyright. All rights reserved.

negative: Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. RECENT FINDINGS: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. SUMMARY: Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.

negative: Convalescent Plasma to Treat COVID-19: Chinese Strategy and Experiences The COVID-19 is currently spreading around the world, which has posed significant threats to global health and economy. Convalescent plasma is confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas, and reported the operability of the treatment by case study.

negative: Recovering from the COVID-19 Pandemic: A Focus on Older Adults As we look toward recovery from the COVID-19 pandemic, we overview challenges to be minimized, including economic setbacks, health and well-being effects, and highlighted ageism, racism, and classism. We articulate opportunities to be seized, including increased comfort with technology and online platforms; stronger family and intergenerational connections, renewed energy to combat social isolation; more respect for self-care and time management; increased awareness about the importance of advance directives; and, potentially, increased interest across disciplines to work on issues of aging society. Ongoing efforts to improve policies and programs for longer, healthier lives might now be more productive, as we communicate to consumers, public officials, and everyday citizens who may be more aware of what isn't working, what is at stake, and what might be improved.

negative: Recovering from the COVID-19 Pandemic: A Focus on Older Adults. As we look toward recovery from the COVID-19 pandemic, we overview challenges to be minimized, including economic setbacks, health and well-being effects, and highlighted ageism, racism, and classism. We articulate opportunities to be seized, including increased comfort with technology and online platforms; stronger family and intergenerational connections, renewed energy to combat social isolation; more respect for self-care and time management; increased awareness about the importance of advance directives; and, potentially, increased interest across disciplines to work on issues of aging society. Ongoing efforts to improve policies and programs for longer, healthier lives might now be more productive, as we communicate to consumers, public officials, and everyday citizens who may be more aware of what isn't working, what is at stake, and what might be improved.

negative: Rising evidence for neurological involvement in COVID-19 pandemic

negative: Acute on Chronic Liver Failure from Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious viral disease that predominantly causes respiratory symptoms. Elevated liver enzymes have been reported during the course of disease and appear to be common. We present a 56-yearold woman with a history of decompensated alcoholic cirrhosis who presented with abdominal pain, fever and diarrhea and was found to have acute on chronic liver failure secondary to SARS-CoV-2 infection. The patient was treated with empiric antibiotic and supportive care with subsequent improvement.

negative: The COVIRL-001 Trial: A multicentre, prospective, randomised trial comparing standard of care (SOC) alone, SOC plus hydroxychloroquine monotherapy or SOC plus a combination of hydroxychloroquine and azithromycin in the treatment of non- critical, SARS-CoV-2 PCR-positive population not requiring immediate resuscitation or ventilation but who have evidence of clinical decline: A structured summary of a study protocol for a randomised controlled trial

negative: Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems. COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation. People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important.

negative: Maternal Death Due to COVID-19 Disease Abstract Background Despite 2.5 million infections and 169,000 deaths worldwide (current as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity had been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and mortal respiratory disease previously documented among pregnant women following other related coronavirus outbreaks (SARS-CoV in 2003 and MERS-CoV) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. Objectives To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. Study design We describe here a multi-institution adjudicated case series from Iran which includes 9 pregnant women diagnosed with severe COVID-19 disease during their latter 2nd or 3rd trimester. All 9 pregnant women were diagnosed with SARS-CoV-2 infection by rRT-PCR nucleic acid testing (NAT). Outcomes of these women were compared to their familial/household members with exposure to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. Results Among 9 pregnant women with severe COVID-19 disease, at the time of reporting 7 of 9 died, 1 of 9 remains critically ill and ventilator-dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance the maternal outcomes were more severe when compared to other high and low-risk familial/household members (n=33 members for comparison). Conclusion We report herein maternal deaths due to COVID-19 disease. Until rigorously collected surveillance data emerges, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed with COVID-19 disease in their latter trimester(s).

negative: Coronavirus Infection in Cats Cats are susceptible to natural infection with several strains of feline coronavirus that result in either effusive and noneffusive feline infectious peritonitis or enteritis. Excretion of coronavirus by infected cats into the environment occurs by way of feces, oronasal secretions, and possibly urine. Clinical diagnosis of coronavirus infection is made by evaluating the case history, physical findings, laboratory results, and coronavirus antibody titers as well as ruling out analogous diseases. An intranasal temperature-sensitive feline infectious peritonitis coronavirus vaccine is available for use in healthy cats 16 weeks of age or older.

negative: Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis Abstract Background In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

negative: COVID-19 pandemic and cardiovascular complications: what have we learned so far?

negative: Analysis of 92 deceased patients with COVID‐19 OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease‐19 (COVID‐19). METHOD: We collected the medical records of 92 patients with COVID‐19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID‐19. CONCLUSION: The main complications of deceased patients with COVID‐19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.

negative: COVID-19 and Shock: A Cautionary Tale for Elderly Patients from a Pooled Analysis

negative: Cardiovascular disease, heart failure and COVID-19

negative: A Roadmap to Reopening a Neurosurgical Practice in the age of COVID-19 Abstract The Coronavirus Disease 2019 (COVID-19) outbreak has left a lasting mark on medicine globally. Here we outline the steps that the Lenox Hill Hospital/Northwell Health Neurosurgery Department—located within the epicenter of the pandemic in New York City—is currently taking to recover our neurosurgical efforts in the age of COVID-19. We outline measurable milestones to identify the transition to the recovery period and hope these recommendations may serve as a framework for an effective path forward. We believe that recovery following the COVID-19 pandemic offers unique opportunities to disrupt and rebuild the historical patient and office experience as we evolve with modern medicine in a post-COVID-19 world.

negative: COVID-19 convalescent plasma transfusion

negative: Characterizing the Impact of COVID-19 on Men Who Have Sex with Men Across the United States in April, 2020 The COVID-19 pandemic is reinforcing health inequities among vulnerable populations, including men who have sex with men (MSM). We conducted a rapid online survey (April 2 to April 13, 2020) of COVID-19 related impacts on the sexual health of 1051 US MSM. Many participants had adverse impacts to general wellbeing, social interactions, money, food, drug use and alcohol consumption. Half had fewer sex partners and most had no change in condom access or use. Some reported challenges in accessing HIV testing, prevention and treatment services. Compared to older MSM, those 15–24 years were more likely to report economic and service impacts. While additional studies of COVID-19 epidemiology among MSM are needed, there is already evidence of emerging interruptions to HIV-related services. Scalable remote solutions such as telehealth and mailed testing and prevention supplies may be urgently needed to avert increased HIV incidence among MSM during the COVID-19 pandemic era. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-02894-2) contains supplementary material, which is available to authorized users.

negative: Coronavirus: Hotspot on coronavirus disease 2019 in India The novel coronavirus disease (COVID-19) or also known as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recognized as the cause of respiratory infection in Wuhan, Hubei Province, China, in late December 2019. As of April 5, 2020, this epidemic had spread to worldwide with 12,03,485 confirmed cases, including 62,000 deaths. The World Health Organization has declared it a Global Public Health Crisis. Coronavirus causes respiratory illness coughing, sneezing, breathlessness, and fever including pneumonia. The disease is transmitted person to person through infected droplets. At present, the research on novel coronavirus is still in the primary stage. Based on the published study, we thoroughly summarize the history and origin, microbiology and taxonomy, mode of transmissions, target receptor, clinical features, diagnosis, prevention, and treatment about COVID-19. This short report writes in hope for providing platform to community and researcher dealings against with the novel coronavirus and providing a reference for further studies.

negative: Natural experiment concept to accelerate the Re-purposing of existing therapeutics for Covid-19 One of the many questions with respect to controlling the novel coronavirus pandemic is whether existing drugs can be re-purposed (re-positioned) for the prevention or treatment of Covid-19 - or for any future epidemic. The usefulness of existing approaches for re-purposing range from computational modeling to clinical trials. These are often time-consuming, resource intensive, and prone to failure. Proposed here is a new but simple concept that would capitalize on the opportunity presented by the on-going natural experiment involving the collection of data from epidemiological surveillance screening and diagnostic testing for clinical treatment. The objective would be to also collect for each Covid-19 case the patient's prior usage of existing therapeutic drugs. These drug usage data would be collected for several major test groups - those who test positive for active SARS-CoV-2 infection (using molecular methods) and those who test negative for current infection but also test positive for past infection (using serologic antibody tests). Patients from each of these groups would also be categorized with respect to where they resided on the spectrum of morbidities (from no or mild symptomology to severe). By comparing the distribution of normalized usage data for each drug within each group, drugs that are more associated with particular test groups could be revealed as having potential prophylactic, therapeutic, or contraindicated effects with respect to disease progression. These drugs could then be selected as candidates for further evaluation in fighting Covid-19. Also summarized are some of the numerous attributes, advantages, and limitations of the proposed concept, all pointing to the need for further discussion and evaluation.

negative: Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression With the emergence of the Novel Coronavirus (2019-nCoV), researchers worldwide have started detecting the probable pathogenesis of the disease. The renin–angiotensin system (RAS) and angiotensin-converting enzymes have received a good deal of attention as possible pathways involved in 2019-nCoV pathogenesis. As the experiments seeking to find potential medications acting on these pathways are being conducted in the early phases, having an ecological worldview on the relationship between the prevalence of COVID-19 disease and the genetic differences in the genes involved in the RAS system could be valuable for the field. In this regard, we conducted a meta-analysis study of the prevalence of ACE (I/D) genotype in countries most affected by the COVID-19. In the meta-analysis, 48,758 healthy subjects from 30 different countries were evaluated in 116 studies, using the Comprehensive Meta-analysis software. The I/D allele frequency ratio was pooled by a random-effect model. The COVID-19 prevalence data of death and recovery rates were evaluated as the latitudes for the meta-regression analysis. Our results demonstrated that with the increase of the I/D allele frequency ratio, the recovery rate significantly increased (point estimate: 0.48, CI 95%: 0.05–0.91, p = 0.027). However, there was no significant difference in the case of death rate (point estimate: 1.74, CI 95%: 4.5–1.04, p = 0.22). This ecological perspective coupled with many limitations does not provide a direct clinical relevance between the COVID-19 and RAS system, but it shows potential pathophysiological associations. Our results raise concerns about ethnic and genetic differences that could affect the effectiveness of the currently investigated RAS-associated medications in different regions.

negative: Everything old is new again: COVID-19 and public health

negative: Crucial Inflammatory Mediators and Efficacy of Drug Interventions in Pneumonia Inflated COVID-19: An Invivo Mathematical Modelling Study The virus SARS-COV-2 caused disease COVID-19 has been declared a pandemic by WHO. Currently, over 210 countries and territories have been affected. Careful, well-designed drugs and vaccine for the total elimination of this virus seem to be the need of the hour. In this context, the invivo mathematical modelling studies can be extremely helpful in understanding the efficacy of the drug interventions. These studies can also help understand the role of the crucial inflammatory mediators and the behaviour of immune response towards this novel coronavirus. Motivated by these facts, in this paper, we study the invivo dynamics of Covid-19. The results obtained here are inline with some of the clinical findings for Covid-19. This invivo modelling study involving the crucial biomarkers of Covid-19 is the first of its kind and the results obtained from this can be helpful to researchers, epidemiologists, clinicians and doctors who are working in this field.

negative: Identification of the severe acute respiratory syndrome coronavirus by simultaneous multigene DNA sequencing. The recent severe acute respiratory syndrome (SARS) outbreak resulted in calls for an accurate diagnostic test that can be used not only for routine testing but also for generating nucleotide sequences to monitor the epidemic. Although the identity of the SARS coronavirus (SARS-CoV) genome was confirmed by DNA sequencing, it is impractical to sequence the entire 29-kb SARS-CoV genome on a routine basis. Therefore, alternative assay methods such as the enzyme-linked immunosorbent assay and PCR have been pursued for routine testing, primarily to resolve probable cases. We report here a modification of standard DNA sequencing technology for accurate identification of SARS-CoV in routine testing. Instead of requiring the sequencing of the whole SARS-CoV genome, our modification enables the simultaneous sequencing of three regions of the SARS-CoV genome, the spike protein-encoding gene (35 nucleotides), gene M (43 nucleotides), and gene N (45 nucleotides), in a single electropherogram. Comparing these nucleotide sequences to DNA databank entries (National Institutes of Health) conclusively identified them as SARS-CoV sequences.

negative: A case report of neonatal COVID-19 infection in China ;Clinical Infectious Diseases ;Oxford Academic Abstract In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread in many countries Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progresse to severe illness We report a case of neonatal COVID-19 infection in China with pharyngeal swabs tested positive by rRT-PCR assay 36 hours after birth However, whether the case is a vertical transmission from mother to child remains to be confirmed

negative: Nosocomial amplification of MERS-coronavirus in South Korea, 2015 BACKGROUND: Nosocomial amplification resulted in nearly 200 cases of Middle East respiratory syndrome (MERS) during the 2015 South Korean MERS-coronavirus outbreak. It remains unclear whether certain types of cases were more likely to cause secondary infections than others, and if so, why. METHODS: Publicly available demographic and transmission network data for all cases were collected from the Ministry of Health and Welfare. Statistical analyses were conducted to determine the relationship between demographic characteristics and the likelihood of human-to-human transmission. Findings from the statistical analyses were used to inform a hypothesis-directed literature review, through which mechanistic explanations for nosocomial amplification were developed. RESULTS: Cases that failed to recover from MERS were more likely to cause secondary infections than those that did. Increased probability of direct, human-to-human transmission due to clinical manifestations associated with death, as well as indirect transmission via environmental contamination (e.g., fomites and indoor ventilation systems), may serve as mechanistic explanations for nosocomial amplification of MERS-coronavirus in South Korea. CONCLUSIONS: In addition to closely monitoring contacts of MERS cases that fail to recover during future nosocomial outbreaks, potential fomites with which they may have had contact should be sanitized. Furthermore, indoor ventilation systems that minimize recirculation of pathogen-bearing droplets should be implemented whenever possible.

negative: Variables influencing radiology volume recovery during the next phase of the COVID-19 pandemic Abstract The COVID-19 pandemic has reduced radiology volumes across the country as providers have decreased elective care in order to minimize the spread of infection and free up health care delivery system capacity. Following the stay-at-home order in our county, imaging volumes at our institution decreased to approximately 46% of baseline volumes, similar to the experience of other radiology practices. Given the substantial differences in severity and timing of the disease in different geographic regions, estimating resumption of radiology volumes will be one of the next major challenges for radiology practices. We hypothesize that there are 6 major variables that will likely predict radiology volumes: (1) severity of disease in the local region, including potential subsequent “waves” of infection, (2) lifting of government social distancing restrictions, (3) patient concern regarding risk of leaving home and entering imaging facilities, (4) management of pent up demand for imaging delayed during the acute phase of the pandemic, including institutional capacity, (5) impact of the economic downturn on health insurance and ability to pay for imaging, and (6) radiology practice profile reflecting amount of elective imaging performed, including type of patients seen by the radiology practice such as emergency/inpatient/outpatient mix and sub-specialty types. We encourage radiology practice leaders to use these and other relevant variables to plan for the coming weeks and to work collaboratively with local health system and governmental leaders to help ensure that needed patient care is restored as quickly as the environment will safely permit.

negative: Equine Coronavirus Infection Equine coronavirus (ECoV) is an emerging virus associated clinically and epidemiologically with fever, depression, anorexia, and less frequently colic or diarrhea in adult horses. Sporadic cases and outbreaks have been reported with increased frequency since 2010 from Japan, the USA, and more recently from Europe. A feco-oral transmission route is suspected, and clinical or asymptomatic infected horses appear to be responsible for direct and indirect transmission of ECoV. A presumptive clinical diagnosis of ECoV infection may be suggested by clinical presentation and hematological abnormalities such as leukopenia due to lymphopenia and/or neutropenia. Confirmation of ECoV infection is provided by specific ECoV nucleic acid detection in feces by quantitative PCR or demonstration of coronavirus antigen by immunohistochemistry or electron microscopy in intestinal biopsy material obtained ante- or postmortem. The disease is generally self-limiting and horses typically recover with symptomatic supportive care. Complications associated with disruption of the gastrointestinal barrier have been reported in some infected horses and include endotoxemia, septicemia, and hyperammonemia-associated encephalopathy. This chapter reviews current knowledge concerning the etiology, epidemiology, clinical signs, diagnosis, pathology, treatment, and prevention of ECoV infection in adult horses.

negative: Virtual Visits for Care of Patients with Heart Failure in the Era of COVID-19: A Statement from the Heart Failure Society of America

negative: Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients Initially, acute loss of smell (anosmia) and taste (ageusia) was not considered important symptoms for coronavirus disease 2019 (COVID-19). To determine the prevalence of these symptoms and to evaluate their diagnostic significance, we (approximately 150 physicians of the Daegu Medical Association) prospectively collected data of cases of anosmia and ageusia from March 8, 2020, via telephone interview among 3,191 patients in Daegu, Korea. Acute anosmia or ageusia was observed in 15.3% (488/3,191) patients in the early stage of COVID-19 and in 15.7% (367/2,342) patients with asymptomatic-to-mild disease severity. Their prevalence was significantly more common among females and younger individuals (P = 0.01 and P < 0.001, respectively). Most patients with anosmia or ageusia recovered within 3 weeks. The median time to recovery was 7 days for both symptoms. Anosmia and ageusia seem to be part of important symptoms and clues for the diagnosis of COVID-19, particularly in the early stage of the disease.

negative: [An epidemiological forecast of COVID-19 in Chile based on the generalized SEIR model and the concept of recovered]. The COVID-19 pandemic declared by the World Health Organization (WHO) has generated a wide-ranging debate regarding epidemiological forecasts and the global implications. With the data obtained from the Chilean Ministry of Health (MINSAL), a prospective study was carried out using the generalized SEIR model to estimate the course of COVID-19 in Chile. Three scenarios were estimated: Scenario 1 with official MINSAL data; scenario 2 with official MINSAL data and recovery criteria proposed by international organizations of health; and scenario 3 with official MINSAL data, recovery criteria proposed by international organizations of health, and without considering deaths in the total recovered. There are considerable differences between scenario 1 compared to 2 and 3 in the number of deaths, active patients, and duration of the disease. Scenario 3, considered the most adverse, estimates a total of 11,000 infected people, 1,151 deaths, and that the peak of the disease will occur in the first days of May. We concluded that the concept of recovered may be decisive for the epidemiological forecasts of COVID-19 in Chile.

negative: COVID-19 and obesity—lack of clarity, guidance, and implications for care

negative: Estimates of the severity of coronavirus disease 2019: a model-based analysis BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. INTERPRETATION: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. FUNDING: UK Medical Research Council.

negative: Management of Acute Myocardial Infarction During the COVID-19 Pandemic Abstract The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a new and lethal disease termed coronavirus disease 2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with COVID-19. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating a ST-elevation MI presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury and the prevalence of COVID-19 disease in the US population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.

negative: Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: A retrospective study Abstract Objectives Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. Methods A retrospective study was performed in non-ICU Ward in Jinyintan Hospital from February 2, 2020 to March 20, 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay for pharyngeal swab specimens. The confirmed patients were divided into umifenovir group and control group according to the use of umifenovir. The main outcomes were the negative rate of pharyngeal swab’s test for SARS-CoV-2 within 1 week after admission, as well as the duration for virus turning negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleid acid of SARS-CoV-2 was negative for 2 consecutive tests. Results A total of 81 COVID-19 patients were included, with 45 in umifenovir group and 36 in control group. Baseline clinical, laboratory characteristics were comparable between two groups. 33/45 (73.3%) patients in umifenovir group were tested negative in SARS-CoV-2 within 7 days after admission, the number was 28/36 (77.8%) in control group (p=0.19). The median time from onset of symtoms to SARS-CoV-2 turning negative were 18 days (interquartile range [IQR] 12-21) in umifenovir group and 16 days (IQR, 11-21) in control group (p= 0.42). Patients in umifenovir group had longer hospital stay than patients in control group (13 days [IQR, 9-17] vs 11 days [IQR, 9-14], p=0.04). No deaths or severe adverse reaction were found in both groups. Conclusions Umifenovir might not improve the prognosis or accelerate the SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir.

negative: EFFECT OF SIALODACRYOADENITIS VIRUS INFECTION ON AXONAL REGENERATION The effect of sialodacryoadenitis virus (SDAV) infection on axonal regeneration and functional recovery was investigated in male Lewis rats. Animals underwent unilateral tibial nerve transection, immediate repair, and treatment with either FK506 (treated) or control vehicle (untreated). Serial walking track analyses were performed to assess functional recovery. Nerves were harvested for morphometric analysis on postoperative day 18 after an SDAV outbreak occurred that affected the 12 experimental animals. Histomorphometry and walking track data were compared against 36 historical controls. Rats infected with SDAV demonstrated severely impaired axonal regeneration and diminished functional recovery. Total fiber counts, nerve density, and percent neural tissue were all significantly reduced in infected animals (P < 0.05). Active SDAV infection severely impaired nerve regeneration and negated the positive effect of FK506 on nerve regeneration in rats. Immunosuppressive risks must be weighed carefully against the potential neuroregenerative benefits in the treatment of peripheral nerve injuries.

negative: Resistance to coronavirus infection in amino peptidase N-deficient pigs The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea virus (PEDV) are sources of high morbidity and mortality in neonatal pigs, a consequence of dehydration caused by the infection and necrosis of enterocytes. The biological relevance of amino peptidase N (ANPEP) as a putative receptor for TGEV and PEDV in pigs was evaluated by using CRISPR/Cas9 to edit exon 2 of ANPEP resulting in a premature stop codon. Knockout pigs possessing the null ANPEP phenotype and age matched wild type pigs were challenged with either PEDV or TGEV. Fecal swabs were collected daily from each animal beginning 1 day prior to challenge with PEDV until the termination of the study. The presence of virus nucleic acid was determined by PCR. ANPEP null pigs did not support infection with TGEV, but retained susceptibility to infection with PEDV. Immunohistochemistry confirmed the presence of PEDV reactivity and absence of TGEV reactivity in the enterocytes lining the ileum in ANPEP null pigs. The different receptor requirements for TGEV and PEDV have important implications in the development of new genetic tools for the control of enteric disease in pigs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11248-018-0100-3) contains supplementary material, which is available to authorized users.

negative: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

negative: Radiotherapy in the time of the Coronavirus pandemic: when less is better

negative: Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China Abstract Background In late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. Methods We performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. Results Of the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

negative: Chest CT features and their role in COVID-19 Since December 2019, the novel coronavirus disease (COVID-19) has spread rapidly throughout China. This article reviews the chest CT features of COVID-19 and analyzes the role of chest CT in this health emergency.

negative: Preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid overview of reviews Background: The overall objective of this rapid overview of reviews (overview hereafter) was to identify evidence from systematic reviews (SRs) for infection control and prevention practices for adults aged 60 years and older in long-term care settings. Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, biorxiv.org/medrxiv.org, clinicaltrials.gov and the Global Infectious Disease Epidemiology Network (GIDEON) were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AMSTAR 2) were carried out by single reviewers. Results: A total of 6 SRs published between 1999 and 2018 were identified and included in the overview. The SRs included between 1 and 37 primary studies representing between 140 to 908 patients. All of the primary studies included in the SRs were carried out in long-term care facilities (LTCF) and examined pharmacological, non-pharmacological, or combined interventions. One high quality SR found mixed results for the effectiveness of hand hygiene to prevent infection (2 studies statistically significant positive results, 1 study non-statistically significant results). One moderate quality SR with meta-analysis found a moderate non-statistically significant effect for personal protective equipment (PPE) in preventing infection and found no statistically significant results for the effectiveness of social isolation. One moderate quality SR reported statically significant evidence for the effectiveness of amantadine and amantadine + PPE to prevent infection with respiratory illness in LTCF. Conclusion: The current evidence suggests that with antiviral chemoprophylaxis with adamantine is effective in managing respiratory illness in residents of long-term care facilities. The rest of the strategies can be used in long-term care facilities, yet have limited evidence supporting their use from systematic reviews.

negative: The Epidemiology of COVID-19 and applying Non Pharmaceutical interventions by using the Susceptible, Infectious Recovered epidemiological Model in Pakistan. Introduction: The COVID-19 is caused by the virus known as sever acute respiratory syndrome corona virus 2 (SARS-CoV-2) having the common symptoms such as Flue, fever, dry cough and shortness of breath. The first case was reported in WUHAN city china in December 2019 and it spread to the whole world, WHO declared as world pandemic on 11th march 2020. SIR Epidemiological Model: The first case in Pakistan was confirmed on 26th Feb 2020 as by the 8th April 2020 the total no of confirmed cases 4187 with 58 deaths and 467 recoveries throughout the country. The upcoming situation of the COVID-19 in Pakistan is forecasted by using SIR epidemiological, which is one of the mathematical derivative models with great accuracy rate prediction used for infectious disease. This model was introduced in the early 20th century. Results: Pakistan is will be having a heavy burden of patients 80000 plus infected patients 45000 recoveries 10000 hospitalized 3000 ICU and 800 plus deaths in the next 20 days. A complete lock down, social distancing and imposing curfew to keep every person at home can save Pakistan from a very huge number 1000000 infected patients with huge number of causalities with next 2 months. Key words: COVID-19, Coronavirus COV2, Pakistan, SIR model

negative: [Impact of complicated myocardial injury on the clinical outcome of severe or critically ill COVID-19 patients]. Objective: To analyze the clinical characteristics of the severe or critically ill patients with novel coronavirus pneumonia (COVID-19), and evaluate the impact of complicated myocardial injury on the prognosis of these patients. Methods: A retrospective study was conducted in 54 patients who admitted to Tongji hospital from February 3, 2020 to February 24, 2020 and met the criteria of severe or critical conditions of COVID-19. The clinical characteristics and hospital mortality rate were analyzed and compared between the patients with or without myocardial injury, which was defined with 3 times higher serum cardiac troponin value. Results: The median age of the 54 patients was 68 (59.8, 74.3) years. Among all the patients, 24 (44.4%) patients were complicated with hypertension, 13 (24.1%) with diabetes, 8 (14.8%) with coronary heart disease, and 3 (5.6%) with previous cerebral infarction. During hospitalization, 24 (44.4%) of the patients were complicated with myocardial injury and 26 (48.1%) patients died in hospital. In-hospital mortality was significantly higher in patients with myocardial injury than in patients without myocardial injury (14 (60.9%) vs. 8 (25.8%), P=0.013). Moreover, the levels of C-reactive protein (153.6 (80.3, 240.7) ng/L vs. 49.8 (15.9, 101.9) ng/L) and N-terminal pro-B-type natriuretic peptide (852.0 (400.0, 2 315.3) ng/L vs. 197.0 (115.3, 631.0) ng/L) were significantly higher than patients without myocardial injury (all P<0.01). Conclusions: Prevalence of myocardial injury is high among severe or critically ill COVID-19 patients. Severe or critically ill COVID-19 patients with myocardial injury face a significantly higher risk of in-hospital mortality. The study suggests that it is important to monitor and manage the myocardial injury during hospitalization for severe or critically ill COVID-19 patients.

negative: Systematic Review of the Registered Clinical Trials of Coronavirus Disease 2019 (COVID-19) Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have immediately carried out clinical research scheme of the COVID-19. But, there is still a lack of systematic review of registered clinical trials. Therefore, we conducted a systematic review of the clinical trials of COVID-19 to summarize the characteristics of the COVID-19 registered clinical trials. Methods: This study is based on the recommendations of the PRISMA in the Cochrane handbook. The databases from the Chinese Clinical Registration Center and the ClinicalTrials.gov were searched to collect the registered clinical trials of COVID-19. The retrieval inception date is February 9, 2020. Two researchers independently selected the literature based on inclusion and exclusion criteria, extracted data and evaluated the risk of bias. Results: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) of COVID-19 were obtained. A majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials had been completed; 34 trials were early clinical exploratory trials or in a pre-experiment stage, 15 trials belonged to phrase Ⅲ and 4 trials were phrase Ⅳ. The methods of intervention included traditional Chinese medicine involving 26 trials, Western medicine involving 30 trials, and integrated traditional Chinese medicine and Western medicine involving 19 trials. The subjects were mainly non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60 - 200), and the median execute time of the trials was 179 d (IQR: 94 - 366 d). The main outcomes were clinical observation and examinations. Overall, both the methodology quality of interventional trials and observational studies were low. Conclusions: Disorderly and intensive clinical trials of COVID-19 using traditional Chinese medicine and western medicine are ongoing or will being carried out in China. However, based on the low methodology quality and small sample size and long studies execute time, we will not be able to obtain reliable, high-quality clinical evidence about COVID-19 treatment in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for the clinical trials of COVID-19 in China.

negative: Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.

negative: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.

negative: Defining high-value information for COVID-19 decision-making Initial projections from the first generation of COVID-19 models focused public attention on worst-case scenarios in the absence of decisive policy action. These underscored the imperative for strong and immediate measures to slow the spread of infection. In the coming weeks, however, as policymakers continue enlisting models to inform decisions on COVID-19, answers to the most difficult and pressing policy questions will be much more sensitive to underlying uncertainties. In this study, we demonstrate a model-based approach to assessing the potential value of reducing critical uncertainties most salient to COVID-19 decision-making and discuss priorities for acquiring new data to reduce these uncertainties. We demonstrate how information about the impact of non-pharmaceutical interventions could narrow prediction intervals around hospitalizations over the next few weeks, while information about the prevalence of undetected cases could narrow prediction intervals around the timing and height of the peak of the epidemic.

negative: Middle East respiratory syndrome The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.

negative: Postoperative Recovery in Frail, Pre-frail, and Non-frail Elderly Patients Following Abdominal Surgery. BACKGROUND The objective of this study is to explore the association between frailty and surgical recovery over a 6-month period, in elderly patients undergoing elective abdominal surgery. METHODS A total of 144 patients were categorized as frail, pre-frail, and non-frail based on five criteria: weight loss, exhaustion, weakness, slowness, and low activity. Recovery to preoperative functional status (activities of daily living (ADL) and instrumental activities of daily living (IADL)), cognition, quality of life, and mental health was assessed at 1, 3, and 6 months postoperatively. A repeated measure logistic regression was used to analyze the effect of frailty on recovery over time. The effect of frailty on hospitalization outcomes was also evaluated. RESULTS Mean age was 78 ± 5 years with 17.4% of patients categorized as frail, 60.4% pre-frail, and 22.2% non-frail. At 6 months, the percent of patients who had recovered to preoperative values were: ADL 90%; IADL 76%; cognition 75.5%; mental health 66%; and quality of life 70%. While more frail patients experienced adverse hospitalization outcomes and fewer had recovered to preoperative functional status, these differences were not found to be statistically significant. Overall, frailty status was not significantly associated with the trajectory of recovery or hospitalization outcomes. CONCLUSION Strong, institutional commitment to quality surgical care, as well as appropriate strategies for older patients, may have mitigated the impact of frailty on recovery. Further research is needed to examine the role of frailty in the surgical recovery process.

negative: Global approaches for global challenges: The possible support of rehabilitation in the management of COVID‐19 We have read with interest the paper by Li and colleagues about the neurotropism of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), responsible of coronavirus disease (COVID-19), recently discovered in China and now worldwide spread.1 In particular, the paper focuses on the role of the nervous system involvement in causing the respiratory failure. This article is protected by copyright. All rights reserved.

negative: Physiotherapists during COVID-19: usual business, in unusual times

negative: COVID-19, SARS and MERS: A neurological perspective Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.

negative: Coronavirus Disease 19 (COVID-19) complicated with pneumonia in a patient with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs In December 2019, numerous coronavirus disease 2019 (COVID-19) cases were reported in Wuhan, China, which has since spread throughout the world. However, its impact on rheumatoid arthritis (RA) patients is unknown. Herein, we report a case of COVID-19 pneumonia in a 61-year-old female RA patient who was receiving conventional disease-modifying antirheumatic drugs (cDMARDs). The patient presented with a 4-day history of myalgia and febrile sensation. COVID-19 was confirmed by real-time polymerase chain reaction (PCR). Chest X-ray showed increased opacity on the right lower lung area, and C-reactive protein level was slightly elevated. The patient was treated with antiviral agents (lopinavir/ritonavir), and treatment with cDMARDs was discontinued except hydroxychloroquine. Her symptoms and laboratory results gradually improved. Three weeks later, real-time PCR for COVID-19 showed negative conversion, and the patient was discharged without any complications.

negative: Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biological treatment and renal transplanted recipients in maintenance immunosuppressive treatment

negative: Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery PURPOSE: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

negative: Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources • COVID-19 mortality rates in Wuhan and Hubei decay exponentially. • COVID-19 mortality rates outside Hubei and Wuhan are nearly constant. • COVID-19 recovery rates in Wuhan and Hubei grow exponentially. • Over 40,000 aided health workers help Hubei to effectively treat patients. • Newly supplied beds allow over 38,000 patients in Wuhan to be treated in hospitals.

negative: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV(1)/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF(25%–75%), t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

negative: Chloroquine paradox may cause more damage than help fight COVID-19 Abstract Novel coronavirus disease 2019 (COVID-19) pandemic is the most recent health care crisis without specific prophylactic or therapeutic drugs. Antimalarial drug chloroquine (CHL) and its safer derivative hydroxychloroquine (HCHL) have been proposed to be repurposed to treat SARS coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. CHL/HCHL have anti-inflammatory activity and are used to treat rheumatoid arthritis, osteoarthritis and lupus. Although, CHL/HCHL have an anti-viral activity against several viruses in cell-cultures, the anti-viral activity in-vivo is questionable. Repurposing of CHL/HCHL to treat SARS-CoV-2 infection is appealing. However, there is empirical evidence from animal studies with other viruses suggesting that CHL/HCHL may have an untoward paradoxical effect. One thus cannot exclude the possibility that CHL may increase the severity of the disease and prove deleterious both for the patients and public health efforts to contain the highly contagious and explosive spread of SARS-CoV-2.

negative: Pre-Clinical and Clinical Efficiency of Complexes of Oligoribonucleotides with D-Mannitol against Respiratory Viruses Oligoribonucleotides-D-mannitol (ORNs-D-M) complexes possess antiviral, anti-inflammatory, and immunomodulatory actions. The aim of the present study was to evaluated an antiviral effect of ORNs-D-M against parainfluenza virus type 3 (PIV3); influenza CA709, PR834; avian influenza virus H5N2 (AIV) in vitro by a TCID(50); hemadsorption and neuraminidase activity assays; and clinical efficiency of ORNs-D-M in patients with acute respiratory infections (ARIs) of various etiologies by PCR assay and AmpliSens test systems. It was observed that ORNs-D-M have an antiviral activity against the influenza CA709, PR834, PIV3, and AIV in vitro. The injectable dosage form of ORNs-D-M was shown to have a stronger antiviral effect compared to capsule form. It was also detected that the injectable form of ORNs-D-M significantly reduced the neuraminidase activity of influenza PR834. A complex treatment of patients with ORNs-D-M had a positive effect on the course of the disease, it accelerated patients’ recovery. Treatment with ORNs-D-M caused eradication of adeno- and influenza viruses in patients with ARI. This drug contributed to significant decrease in duration of febrile period and cough. Comprehensive treatment with ORNs-D-M improved the disease clinical findings significantly. Collectively, these results suggested that ORNs-D-M may be used at co-infection with influenza and other respiratory viruses as a medical antiviral drug.

negative: [An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19]. OBJECTIVE To identify the biomarkers as early warning signals for severe COVID-19. METHODS We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS An increased NLR can serve as an early warning signal of severe COVID-19.

negative: Distribution of Transmission Potential during Non-Severe COVID-19 Illness BACKGROUND: Patients recovering from coronavirus disease 2019 (COVID-19) often continue to test positive for the causative virus by PCR even after clinical recovery, thereby complicating return-to-work plans. The purpose of this study was to evaluate transmission potential of COVID-19 by examining viral load with respect to time. METHODS: Health care personnel (HCP) at Cleveland Clinic diagnosed with COVID-19, who recovered without needing hospitalization, were identified. Threshold cycle (Ct) for positive PCR tests were obtained and viral loads calculated. Association of viral load with days since symptom onset was examined in a multivariable regression model, which was reduced by stepwise backward selection to only keep variables significant at a level of 0.05. Viral loads by day since symptom onset were predicted using the model and transmission potential evaluated by examination of a viral load-time curve. RESULTS: Over six weeks, 230 HCP had 528 tests performed. Viral loads declined by orders of magnitude within a few days of symptom onset. The only variable significantly associated with viral load was time since onset of symptoms. Of the area under the curve (AUC) spanning symptom onset to 30 days, 96.9% lay within the first 7 days, and 99.7% within 10 days. Findings were very similar when validated using split-sample and 10-fold cross-validation. CONCLUSIONS: Among patients with non-severe COVID-19, viral loads in upper respiratory specimens peak by two or three days from symptom onset and decrease rapidly thereafter. The vast majority of the viral load-time AUC lies within 10 days of symptom onset.

negative: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.

negative: Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review Background: The World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored. Methods: A thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds. Results: Estimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs.

negative: Transparency and information sharing could help abate the COVID-19 pandemic

negative: Coronaviruses Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.

negative: SARS – CoV -2: reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis) Abstract The novel coronavirus COVID-19 follows transmission route and clinical presentation of all community-acquired coronaviruses. Instead, the rate of transmission is significative higher, with a faster spread of the virus responsible of the worldwide outbreak and a significative higher mortality rate due to the development of a severe lung injury. Most noteworthy is the distribution of death rate among age groups. Children and younger people are almost protected from severe clinical presentation. Possible explanation of this phenomenon could be the ability of past vaccinations (especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis) to stimulate immune system and to generate a scattered immunity against non-self antigens in transit, as coronaviruses and other community-circulating viruses and make immune system readier to develop specific immunity against COVID-19. The first support to this hypothesis is the distribution of mortality rate during historical pandemics (“Spanish flu” 1918, “Asian flu” 1956 and “the Hong Kong flu” 1968) among age groups before and after the introduction of vaccines. The immunological support to the hypothesis derives from recent studies about immunotherapy for malignancies, which propose the use of oncolytic vaccines combined with toxoids in order to exploit CD4+ memory T cell recall in supporting the ongoing anti-tumour response. According to this hypothesis vaccine formulations (tetanus, diphtheria, Bordetella pertussis) could be re-administrate after the first contact with Covid-19, better before the development of respiratory severe illness and of course before full-blown ARDS (Acute Respiratory Distress Syndrome). The CD4+ memory exploiting could help immune system to recall immunity of already know antigens against coronaviruses, avoiding or limiting “lung crash” until virus specific immunity develops and making it faster and prolonged. Finally, this administration could be helpful not only in already infected patients, but also before infection. In fact, people could have an immune system more ready when the contact with the COVID-19 will occur.

negative: Treatment considerations for coronavirus (COVID-19)

negative: Acute Myocardial Injury of Patients with Coronavirus Disease 2019 Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.

negative: The Case for a Temporary COVID-19 Income Tax Levy Now, During the Crisis

negative: Viral respiratory infections in elderly patients and patients with chronic obstructive pulmonary disease Abstract Patients with chronic obstructive pulmonary disease (COPD) and elderly individuals are prone to the development of significant lower respiratory tract symptoms from colds caused by viral respiratory pathogens. Longitudinal surveillance studies conducted to assess the impact of viral respiratory tract pathogens on morbidity and mortality in each of these at-risk populations demonstrate that there is a substantial burden of disease from viral respiratory infection (VRI), including rhinovirus infections, with respect to utilization of health-care resources. Despite a similar rate of occurrence of VRI among subjects with COPD and the control group, a cohort with moderate to severe COPD had a 2-fold increase in medical resource utilization, including clinician visits, emergency center visits, and hospitalizations. In surveillance studies of respiratory viruses in the elderly, regular seasonal infections with rhinoviruses cause substantial morbidity, which has been largely underappreciated and underreported.

negative: Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19. Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes. Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients

negative: Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations Abstract This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with confirmed or suspected COVID-19.

negative: A model to forecast regional demand for COVID-19 related hospital beds COVID-19 threatens to overwhelm hospital facilities throughout the United States. We created an interactive, quantitative model that forecasts demand for COVID-19 related hospitalization based on county-level population characteristics, data from the literature on COVID-19, and data from online repositories. Using this information as well as user inputs, the model estimates a time series of demand for intensive care beds and acute care beds as well as the availability of those beds. The online model is designed to be intuitive and interactive so that local leaders with limited technical or epidemiological expertise may make decisions based on a variety of scenarios. This complements high-level models designed for public consumption and technically sophisticated models designed for use by epidemiologists. The model is actively being used by several academic medical centers and policy makers, and we believe that broader access will continue to aid community and hospital leaders in their response to COVID-19. Link to online model: https://surf.stanford.edu/covid-19-tools/covid-19/

negative: Rhabdomyolysis as Potential Late Complication Associated with COVID-19 We describe a patient in Wuhan, China, with severe acute respiratory syndrome coronavirus 2 infection who had progressive pulmonary lesions and rhabdomyolysis with manifestations of lower limb pain and fatigue. Rapid clinical recognition of rhabdomyolysis symptoms in patients with severe acute respiratory syndrome coronavirus 2 infection can be lifesaving.

negative: Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China Objective. A novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China. Methods. In this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome. Results. Among enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458-15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patient's condition, which is conducive to the transformation from severe to mild. Conclusion. In summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.

negative: Predicting Illness Severity and Short-Term Outcomes of COVID-19: A Retrospective Cohort Study in China Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4(+) lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age ≥ 55 years, BMI > 27 kg / m(2), IL-6 ≥ 20 pg / ml, CD4(+) T cell ≤ 400 count / μ L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.

negative: Antiviral therapy in management of COVID-19: a systematic review on current evidence BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.

negative: Coronavirus: Short‐term pain but strong rebound likely ▪ Attention has understandably focused on limiting the damage from the short‐term effects of the coronavirus outbreak. But it's likely that, once disruption and uncertainty fade, the rebound in activity will be strong. It's important for firms to position themselves for such a recovery. ▪ Historical evidence supports this view. In the past 200 years, short recessions have typically been followed by robust recovery. Long‐term impacts from natural disasters have generally only been evident for specific hazards. Except for AIDS, longer‐term pandemic effects also appear to have been contained. ▪ Surveys during the 2003 SARS and 2009 influenza outbreaks highlight one explanation for time‐limited impacts. Public fears increased alongside rising infection rates, but they dissipated promptly as outbreaks came under control. ▪ Our modelling is consistent with these stylised facts. In our coronavirus pandemic scenario, global growth grinds to a halt in Q2 2020 but then rebounds to a rapid pace within a year. With much of the initial output loss recovered in a relatively short period of time, long‐term impacts are limited. ▪ But there are risks to this view. The period of disruption could be longer than anticipated, depending on the potential spread and seasonality of COVID‐19 and policy actions to mitigate the fallout. Opinion polls also highlight the potential risk of larger, more persistent effects for some countries. ▪ Moreover, coronavirus‐related weakness and associated financial distress could expose other key vulnerabilities ‐ for example related to deteriorating corporate sector balance sheets and fragile trade relations. These would be expected to have persistent effects on global activity over the coming years.

negative: SAveRUNNER: a network-based algorithm for drug repurposing and its application to COVID-19 The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity, comorbidity, or for their association to drugs tentatively repurposed to treat COVID-19. Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments, as well as a new combination therapy of 5 drugs, actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies, and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.

negative: Has COVID-19 played an unexpected “stroke” on the chain of survival? Abstract Background The COVID-19 pandemics required several changes in stroke management and it may have influenced some clinical or functional characteristics. We aimed to evaluate the effects of the COVID-19 pandemics on stroke management during the first month of Italy lockdown. In addition, we described the emergency structured pathway adopted by an Italian University Hub Stroke Unit in the cross-border Italy-Slovenia area. Methods We analyzed admitted patients' clinical features and outcomes between 9th March 2020 and 9th April 2020 (first month of lockdown), and compared them with patients admitted during the same period in 2019. Results Total admissions experienced a reduction of 45% during the lockdown compared to the same period in 2019 (16 vs 29, respectively), as well as a higher prevalence of severe stroke (NIHSS>10) at admission (n = 8, 50% vs n = 8, 28%). A dramatic prevalence of stroke of unknown symptom onset was observed in 2020 (n = 8, 50% vs n = 3, 10%). During lockdown, worse functional and independence outcomes were found, despite the similar proportion of reperfused patients. Similar ‘symptoms alert-to-admission’ and ‘door-to-treatment’ times were observed. During lockdown hospitalization was shorter and fewer patients completed the stroke work-up. Conclusion In conclusion, the adopted strategies for stroke management during the COVID-19 emergency have suggested being effective, while suffering a reduced and delayed reporting of symptoms. Therefore, we recommend raising awareness among the population against possible stroke symptoms onset. Thus, think F.A.S.T. and do not stay-at-home at all costs.

negative: 2019 Novel Coronavirus Infection: Gastrointestinal Manifestations The world is witnessing a major public health crisis in the wake of the third coronavirus strain pandemic, a novel coronavirus (severe acute respiratory syndrome coronavirus 2). Although initially thought to be a pure respiratory pathogen, recent reports have highlighted not only the extrapulmonary effects of the virus but also, importantly, the gastrointestinal tract (GIT) effects. Various studies have looked into the effects of this novel coronavirus infection (coronavirus-19 disease [COVID-19]) on GIT involvement with reports of more frequent involvement than previously expected. With feco-oral transmission, debate being conclusively proven with fecal samples testing positive for COVID-19 and longer shedding time, it only underlines the importance of GIT involvement. Moreover, the presence of other GI diseases, such as inflammatory bowel disease, with COVID-19 infection might wreak havoc leading to poor patient outcomes.

negative: Epidemiology and clinical features of coronavirus disease 2019 in children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.

negative: Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade Here, we review the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, including acute kidney injury, and examine the potential effects of ARBs on the outcomes of patients with COVID-19. Lastly, we discuss the clinical management of COVID-19 patients with existing chronic renal disorders, particularly those in dialysis and with kidney transplants.

negative: A Role for Metal-Based Drugs in Fighting COVID-19 Infection? The Case of Auranofin

negative: Chapter 5 Common Myths and Legends of Rabies Abstract Humankind has somewhat of a dark, yet almost fascinating, supernatural relationship with rabies. Even after Pasteur's rabies vaccine discovery, globally people continue to be stricken with it today. History has carried along the myths and legends that surround this diabolical virus. Some still believe that rabies treatment requires 20 or more shots to the stomach by some monstrously long needle. However, today's treatment regimen is typically only four vaccinations (five for immunocompromised) in the arm, plus human rabies immune globulin. This chapter explores the misunderstood concepts of rabies prevalence, signs and symptoms, exposures, and treatment protocols.

negative: Acute Kidney Injury in Hospitalized Patients with COVID-19 Importance: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. Objective: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. Design: Observational, retrospective study. Setting: Admitted to hospital between February 27 and April 15, 2020. Participants: Patients aged [≥]18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. Results: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. Conclusions and Relevance: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.

negative: Posttraumatic stress symptoms of health care workers during the corona virus disease 2019 Corona virus disease 2019 (COVID‐19) outbreak has attracted worldwide attention. The COVID‐19 outbreak is unique in its rapid transmission and results in heavy stress for the front‐line health care workers (HCWs). The current study aimed to exam posttraumatic stress symptoms (PTSSs) of HCWs fighting for the COVID‐19 and to evaluate their sleep quality after 1‐month stressful suffering. Three hundred seventy‐seven HCWs working in different provinces of China participated in the survey between February 1 and 5. The demographic information was collected first. Posttraumatic Stress Disorder Checklist for DSM‐5 (PCL‐5) and the Pittsburgh Sleep Quality Index (PSQI) were selected to measure PTSSs and sleep quality. Results showed that 1 month after the outbreak, the prevalence of PTSSs was 3.8% in HCWs. Female HCWs were more vulnerable to PTSSs with hazard ratio of 2.136 (95% CI = 1.388–3.286). HCWs with higher exposure level also significantly rated more hyperarousal symptoms (hazard ratio = 4.026, 95% CI = 1.233–13.140). There was a significant difference of sleep quality between participants with and without PTSSs (z value = 6.014, p < .001) and among different groups with various contact frequencies (chi‐square = 7.307, p = .026). Path analysis showed that there was a significant indirect effect from exposure level to PTSSs through sleep quality (coefficient = 1.750, 95% CI of Boostroop test = 0.543–2.998). In summary, targeted interventions on sleep contribute to the mental recovery during the outbreak of COVID‐19. Understanding the mental health response after a public health emergency might help HCWs and communities prepare for a population's response to disaster.

negative: A data first approach to modelling Covid-19 The primary data for Covid-19 pandemic is in the form of time series for the number of confirmed, recovered and dead cases. This data is updated every day and is available for most countries from multiple sources. In this work we present a two step procedure for model fitting to Covid-19 data. In the first step, time dependent transmission coefficients are constructed directly from the data and, in the second step, measures of those (minimum, maximum, mean, median etc.,) are used to set priors for fitting models to data. We call this approach a "data driven approach" or "data first approach". This scheme is complementary to Bayesian approach and can be used with or without that for parameter estimation. We use the procedure to fit a set of SIR and SIRD models, with time dependent contact rate, to Covid-19 data for a set of 45 most affected countries. We find that SIR and SIRD models with constant transmission coefficients cannot fit Covid-19 data for most countries (mainly because social distancing, lockdown etc., make those time dependent). We find that any time dependent contact rate, which falls gradually with time, can help to fit SIR and SIRD models for most of the countries. We also present constraints on transmission coefficients and basic reproduction number R0~ as well as effective reproduction number R(t). The main contributions of our work are as follows. (1) presenting a two step procedure for model fitting to Covid-19 data (2) constraining transmission coefficients as well as R0~ and R(t), for a set of most affected countries and (3) releasing a python package PyCov19 that can used to fit a set of compartmental models with time varying coefficients to Covid-19 data.

negative: 2264. The Burden of Respiratory Viral Illness in HIV-Infected Patients BACKGROUND: Among individuals living with human immunodeficiency virus (HIV), pulmonary complications are the most frequent cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described etiologies of lung disease, the role of respiratory viruses remains poorly understood. We sought to describe the burden of respiratory viral illness in HIV-infected inpatients admitted to our tertiary care center. METHODS: All HIV-infected inpatients from August 2015 to March 2018 were approached if they presented with respiratory symptoms, defined as cough, dyspnea, sore throat, rhinorrhea, wheezing, or stridor. Eighty patients were enrolled. After obtaining informed consent, nasopharyngeal swabs and blood were collected. If the subject underwent bronchoscopy per the treating physician, excess bronchoalveolar lavage (BAL) sample was collected. Demographic and clinical data were recorded for each subject. Multiplex PCR testing of all respiratory samples was performed. RESULTS: Of the 70 HIV-infected patients that have undergone complete analysis, 23 (33%) tested positive for respiratory viruses. Of these, 11 (48%) were positive for rhinovirus, 3 were positive for influenza A (13%), 2 for parainfluenza 3 (9%), 2 for coronavirus (9%), and one each tested positive for adenovirus, parainfluenza 4, respiratory syncytial virus and influenza B. One patient had co-infection with rhinovirus and human metapneumovirus. Patients infected with a respiratory virus had severe illness as nearly half (10/23; 48%) required intensive care, 5 (22%) required mechanical ventilation, 4 (17%) were discharged to a higher level of care, and 3 (13%) died. CONCLUSION: The role of respiratory viruses on the lung health of HIV-infected patients is poorly defined. In this study, respiratory viruses were identified in over a third of HIV-infected inpatients, representing a substantial disease burden. Moreover, these patients demonstrated significant disease severity. Given these findings, there is a need for future studies of viral infections in HIV-infected individuals to elucidate mechanisms of susceptibility to reduce the burden of pulmonary morbidity in this vulnerable population. DISCLOSURES: All authors: No reported disclosures.

negative: A special case of COVID-19 with long duration of viral shedding for 49 days Prolonged viral shedding is associated with severe status and poor prognosis of COVID-19 patients. Unexpectedly, here we report a non-severe patient with the longest duration of viral shedding. According to the investigation on the clinical and epidemiological information of this case, we concluded that this type of virus might have a low toxicity and transmissibility, but have a prolonged infective ability and was hardly to be eliminated in the body with regular therapy. However, infusion of plasma from recovered patients showed high efficiency in elimination of this virus. Our findings might shed light on the management of COVID-19.

negative: Cardiac complications in community-acquired pneumonia and COVID-19 Community-acquired pneumonia (CAP) remains a global health problem with significant morbidity and mortality. Much recent published literature about the infection has indicated that a substantial number of patients with CAP, particularly those ill enough to be admitted to hospital, will suffer a cardiovascular event. While these may include events such as deep venous thrombosis and stroke, most of the events involve the heart and include the occurrence of an arrhythmia (most commonly atrial fibrillation), new onset or worsening of heart failure and acute myocardial infarction. While such cardiac events may occur, for example, in all-cause CAP and CAP due to influenza virus infection, and more recently described with the SARS-CoV-2 pandemic, a significant amount of research work has been investigating the pathogenic mechanisms of these cardiac events in patients with CAP due to Streptococcus pneumoniae (pneumococcus) and, more recently, COVID-19 infections. Such research has identified a number of mechanisms by which these microorganisms may cause cardiovascular events. Importantly, these cardiac events appear not only to be associated with in-hospital mortality, but they also appear to contribute to longer-term mortality of patients with CAP, even after their discharge from hospital. This review will focus initially on studies of cardiovascular events in all-cause CAP and pneumococcal CAP, excluding COVID-19 infection, and then address similar issues in the latter infection.

negative: Susceptible-Infected-Recovered (SIR) Dynamics of COVID-19 and Economic Impact I estimate the Susceptible-Infected-Recovered (SIR) epidemic model for Coronavirus Disease 2019 (COVID-19). The transmission rate is heterogeneous across countries and far exceeds the recovery rate, which enables a fast spread. In the benchmark model, 28% of the population may be simultaneously infected at the peak, potentially overwhelming the healthcare system. The peak reduces to 6.2% under the optimal mitigation policy that controls the timing and intensity of social distancing. A stylized asset pricing model suggests that the stock price temporarily decreases by 50% in the benchmark case but shows a W-shaped, moderate but longer bear market under the optimal policy.

negative: Knowledge and practice of preventive measures against COVID-19 infection among pregnant women in a low-resource African setting Background: Coronavirus disease pandemic has resulted in death of thousands of people across several countries. Several preventive measures have been recommended to halt the spread of the disease and its associated mortality. However, the level knowledge and practice of these preventive measures against COVID-19 infection among pregnant women, which constitute vulnerable groups, are yet to be evaluated. Aim: To determine the knowledge and practice of preventive measures against COVID-19 infection among pregnant women in Abakaliki. Materials and Methods: This was a self-administered questionnaire-based cross-sectional study conducted from February 1, 2020 to March 31, 2020 among 284 antenatal clinic attendees at Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State. A pretested and validated questionnaire was used to collect the data. Data analysis was done using SPSS version 22. Results: Of 284 participants, 60.9% (n=173) had adequate knowledge of the preventive measures against COVID-19 infection. However, the overall practice of these preventive measures among the participants were poor as 69.7% of the participants were not practicing the preventive measures against the coronavirus. The determinants of poor practice of the preventive measures among the participants were being in age group 31-40 years (AOR=2.04, 95%CI: 1.26 - 5.37, p=0.022), married (AOR=2.99, 95%CI: 1.40 - 6.33, p=0.035) grandmultiparous (AOR=3.11, 95%CI: 1.32 - 6.56, p=0.021), residing in rural area (AOR=2.08, 95%CI: 1.32 - 4.05, p=0.031), and having no formal education (AOR=6.73, 95%CI: 2.66 - 18.34, p=0.002). Conclusion: The study showed that most of the participants had adequate knowledge of preventive measures against COVID-19 infection but the practice of these preventive measures were poor among the participants.

negative: Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series. OBJECTIVE A pandemic afflicts the entire world. The highly contagious SARS-CoV-2 virus originated in Wuhan, China in late 2019 and rapidly spread across the entire globe. According to the World Health Organization (WHO), the novel Coronavirus (COVID-19)has infected more than two million people worldwide, causing over 160,000 deaths. Patients with COVID-19 disease present with a wide array of symptoms, ranging from mild flu-like complaints to life threatening pulmonary and cardiac complications. Older people and patients with underlying disease have an increased risk of developing severe acute respiratory syndrome (SARS) requiring mechanical ventilation. Once intubated, mortality increases exponentially. A number of pharmacologic regimens, including hydroxychloroquine-azithromycin, antiviral therapy (eg, remdesevir), and anti-IL-6 agents (e.g., toclizumab), have been highlighted by investigators over the course of the pandemic, based on the therapy's potential to interrupt the viral life-cycle of SARS-CoV-2 or preventing cytokine storm. At present, there have been no conclusive series of reproducible randomised clinical trials demonstrating the efficacy of any one drug or therapy for COVID-19. CASES COVID-19 positive patients (n=5) at a single institution received hyperbaric oxygen therapy (HBOT) between 13 and 20 April 2020. All the patients had tachypnoea and low oxygen saturation despite receiving high FiO2. HBOT was added to prevent the need for mechanical ventilation. A standard dive profile of 2.0ATA for 90 minutes was employed. Patients received between one and six treatments in one of two dedicated monoplace hyperbaric chambers. RESULTS All the patients recovered without the need for mechanical ventilation. Following HBOT, oxygen saturation increased, tachypnoea resolved and inflammatory markers fell. At the time of writing, three of the five patients have been discharged from the hospital and two remain in stable condition. CONCLUSION This small sample of patients exhibited dramatic improvement with HBOT. Most importantly, HBOT potentially prevented the need for mechanical ventilation. Larger studies are likely to define the role of HBOT in the treatment of this novel disease.

negative: The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis ABSTRACT IMPORTANCE Coronavirus disease 2019 (COVID-19) is a global pandemic associated with high mortality and effective treatment to prevent clinical deterioration to severe pneumonia has not yet been well clarified. OBJECTIVE To investigate the role of several adjuvant treatments in preventing severe pneumonia in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS Multicenter, retrospective cohort study of 564 consecutively hospitalized patients with confirmed COVID-19 at Third Xiangya Hospital of Central South University, Changsha Public Health Treatment Center, First Hospital of Yueyang, Junshan People's Hospital of Yueyang, Central Hospital of Shaoyang, Central Hospital of Xiangtan, Second Hospital of Changde, Central Hospital of Loudi, and First Affiliated Hospital of University of South China in Hunan province from January 17, 2020 to February 28, 2020; The final date of follow-up was March 15, 2020. EXPOSURES Nonspecific antivirals (arbidol, lopinavir/ritonavir, and interferon α), antihypertensives, and chloroquine. MAIN OUTCOMES AND MEASURES The development of severe COVID-19 pneumonia; Demographic, epidemiological, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS Of 564 patients, the median age was 47 years (interquartile range, 36-58 years), and 284 (50.4%) patients were men. Sixty-nine patients (12.2%) developed severe pneumonia. Patients who developed severe pneumonia were older (median age of 59 and 45 years, respectively), and more patients had comorbidities including hypertension (30.4% and 12.3%, respectively), diabetes (17.4% and 6.7%, respectively), and cardiovascular disease (8.7% and 3.2%, respectively) and presented with fever (84.1% and 60.4%, respectively) and shortness of breath (10.1% and 3.8%, respectively) compared with those who did not. Nonspecific antiviral therapy did not prevent clinical progression to severe pneumonia, although fewer hypertensive patients on angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB) therapy developed severe pneumonia in contrast with those on non-ACEI/ARB antihypertensive therapy (1 of 16 [6.3%] patients and 16 of 49 [32.7%] patients, respectively [difference, 26.4%; 95% CI, 1.5% to 41.3%]). Multivariate logistic regression analysis showed that hypertension without receiving ACEI/ARB therapy was an independent risk factor (odds ratio [OR], 2.07; 95% CI, 1.07 to 4.00) for developing severe pneumonia irrespective of age. Besides, none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching. CONCLUSIONS AND RELEVANCE Hypertensive patients on ACEI or ARB may be protective from severe pneumonia in COVID-19 and hence these therapies should not be ceased unless there is a strong indication or further epidemiological evidence. Though none of the current antiviral and immunoregulation therapy showed benefit in preventing COVID-19 progression, chloroquine deserved further investigation.

negative: COVID-19: the virus in the control of culture?

negative: Caring for our cancer patients in the wake of COVID-19 In response to our current global pandemic, unprecedented healthcare changes may have significant consequences for cancer patients in the United Kingdom. We explore why cancer patients may be more susceptible to severe infection and complications, highlighting various interventions that may help to ensure continuity of care in this unique cohort.

negative: Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19 Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with Corona Virus Disease 2019 (COVID-19), we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. Food and Drug Administration (FDA) approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P<0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

negative: Fatalism in the context of COVID-19: Perceiving coronavirus as a death sentence predicts reluctance to perform recommended preventative behaviors() To manage the spread of coronavirus, health entities have urged the public to take preventative measures such as social distancing and handwashing. Yet, many appear reluctant to take these measures. Research is needed to understand factors underlying such reluctance, with the aim of developing targeted health interventions. We identify associating coronavirus with death as one such factor. 590 participants completed surveys in mid-March 2020, which included attitudes toward coronavirus, preventative behavioral intentions, and sociodemographic factors. Associating coronavirus with death negatively predicted intentions to perform preventative behaviors. Further, associating coronavirus with death was not evenly distributed throughout the sample and was related with a number of sociodemographic factors including age, race, and availability of sick leave. Following recommended preventative measures to slow the spread of coronavirus appears to relate to the degree to which people associate coronavirus with death. These findings can be used by public health researchers and practitioners to identify those for whom targeted health communication and interventions would be most beneficial, as well as to frame health messaging in ways that combat fatalism.

negative: Preparation and evaluation of anti-SARS coronavirus IgY from yolks of immunized SPF chickens Abstract Severe acute respiratory syndrome (SARS) is a recently discovered viral disease, characterized by fever, cough, acute fibrinous pneumonia and high infectivity. Specific pathogen-free (SPF) chickens were immunized with inactivated SARS coronavirus and their eggs were harvested at regular intervals. Yolk immunoglobulin (IgY) was extracted using the water dilution method, followed by further purification on a Sephadex G-75 column. SDS-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot and neutralization test results showed that the IgY obtained was of a high purity and had a strong reactive activity with a neutralization titer of 1:640. Lyophilization and stability tests showed that lyophilized anti-SARS coronavirus IgY had promising physical properties, with no significant reduction in reactive activity and good thermal stability. All these data suggest that the anti-SARS coronavirus IgY could be a new useful biological product for specific antiviral therapy against SARS.

negative: A review of potential treatments to date in COVID-19 patients according to the stage of the disease Abstract Introduction and motivation: Since the end of 2019, the COVID-19 pandemic has affected millions of people worldwide. With the rapid spread of this virus, an immense burden has fallen upon both healthcare and economic systems. As a consequence, there is an unprecedented urgency for researchers and scientific committees from all over the world to find an effective treatment and vaccine. Review Structure: Many potential therapies are currently under investigation, with some, like Hydroxychloroquine, being authorized for emergency use in some countries. The crucial issue is now clearly to find the suitable treatment strategy for patients given comorbidities and the timeline of the illness.Vaccines are also under development and phase 1 clinical trials are rolling. Despite all efforts, no single drug or vaccine has yet been approved. In this review, we aim at presenting the proposed pathophysiological mechanisms of SARS-CoV-2 and to provide clinicians with a brief and solid overview of the current potential treatments classified according to their use at the three different currently proposed disease stages. In light of pathogenesis and proposed clinical classification, this review’s purpose is to summarize and simplify the most important updates on the management and the potential treatment of this emergent disease.

negative: Acute Care Surgery during the COVID-19 pandemic in Spain: changes in volume, causes and complications. A multicentre retrospective cohort study BACKGROUND: during the COVID-19 pandemic, the number of Acute Care Surgery procedures performed in Spanish hospitals decreased significantly. The aim of this study was to compare Acute Care Surgery activity during the COVID-19 pandemic and during a control period. MATERIAL AND METHODS: a multicenter retrospective cohort study was performed including patients who underwent Acute Care Surgery in three tertiary care hospitals in Spain during a control (11(th) March 2019 to 21(st) April 2019) and a pandemic (16(th) March 2020 to 26(th) April 2020) period. Type of surgical procedures, patients´ features and postoperative complications were compared. RESULTS: two hundred and eighty-five and 117 patients were included in each group. Mean number of patients who underwent Acute Care Surgery during the control and pandemic periods was 2.3 and 0.9 patients per day and hospital (p<0.001), representing a 58.9% decrease in Acute Care Surgery activity. Time from symptoms onset to patient arrival at the Emergency Department was longer during the pandemic (44.6 vs. 71.0 hours, p<0.001). Surgeries due to acute cholecystitis and complications from previous elective procedures decreased (26.7% vs. 9.4%) during the pandemic, while bowel obstructions and abdominal wall hernia surgeries increased (12.3% vs. 22.2%) (p=0.001). Morbidity was higher during pandemic period (34.7% vs. 47.1%, p=0.022), although this difference was not statistically significant in the multivariate analysis. Reoperation rate (17.9% vs. 12.8%, p=0.212) and mortality (6.7% vs. 4.3%, p=0.358) were similar in both groups. CONCLUSION: during the COVID-19 pandemic, a significant reduction in the performance of Acute Care Surgery procedures was observed. Moreso, a longer time from symptoms onset to patient arrival at the Emergency Department was noted. Higher morbidity was observed in patients undergoing Acute Care Surgery during the pandemic period, although there was not any difference in mortality or reoperation rate.

negative: Main factors influencing recovery in MERS Co-V patients using machine learning Abstract Background Middle East Respiratory Syndrome (MERS) is a major infectious disease which has affected the Middle Eastern countries, especially the Kingdom of Saudi Arabia (KSA) since 2012. The high mortality rate associated with this disease has been a major cause of concern. This paper aims at identifying the major factors influencing MERS recovery in KSA. Methods The data used for analysis was collected from the Ministry of Health website, KSA. The important factors impelling the recovery are found using machine learning. Machine learning models such as support vector machine, conditional inference tree, naïve Bayes and J48 are modelled to identify the important factors. Univariate and multivariate logistic regression analysis is also carried out to identify the significant factors statistically. Result The main factors influencing MERS recovery rate are identified as age, pre-existing diseases, severity of disease and whether the patient is a healthcare worker or not. In spite of MERS being a zoonotic disease, contact with camels is not a major factor influencing recovery. Conclusion The methods used were able to determine the prime factors influencing MERS recovery. It can be comprehended that awareness about symptoms and seeking medical intervention at the onset of development of symptoms will make a long way in reducing the mortality rate.

negative: COVID-19 in Older People: A Rapid Clinical Review INTRODUCTION: The COVID-19 pandemic poses a high risk to older people. The aim of this paper is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: We searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20th and 24th March 2020, respectively. RESULTS: Screening of over 1100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral-PCR and serology are the mainstays of testing but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: Given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.

negative: De Novo Status Epilepticus in patients with COVID‐19 Neurological complications are increasingly recognized with SARS CoV‐2, the causative pathogen for COVID‐19. We present a single‐center retrospective case series reporting the EEG and outcome of de novo status epilepticus (SE) in two African‐American women with laboratory‐confirmed SARS CoV‐2 virus. SE was the initial presentation in one asymptomatic individual. Patient 2 had COVID‐19 pneumonia, and fluctuating mental status that raised the suspicion of subclinical SE. The patient with older age and higher comorbidities failed to recover from the viral illness that has no definitive treatment.

negative: The scientific literature on Coronaviruses, COVID-19 and its associated safety-related research dimensions: A scientometric analysis and scoping review Abstract The COVID-19 global pandemic has generated an abundance of research quickly following the outbreak. Within only a few months, more than a thousand studies on this topic have already appeared in the scientific literature. In this short review, we analyse the bibliometric aspects of these studies on a macro level, as well as those addressing Coronaviruses in general. Furthermore, through a scoping analysis of the literature on COVID-19, we identify the main safety-related dimensions that these studies have thus far addressed. Our findings show that across various research domains, and apart from the medical and clinical aspects such as the safety of vaccines and treatments, issues related to patient transport safety, occupational safety of healthcare professionals, biosafety of laboratories and facilities, social safety, food safety, and particularly mental/psychological health and domestic safety have thus far attracted most attention of the scientific community in relation to the COVID-19 pandemic. Our analysis also uncovers various potentially significant safety problems caused by this global health emergency which currently have attracted only limited scientific focus but may warrant more attention. These include matters such as cyber safety, economic safety, and supply-chain safety. These findings highlight why, from an academic research perspective, a holistic interdisciplinary approach and a collective scientific effort is required to help understand and mitigate the various safety impacts of this crisis whose implications reach far beyond the bio-medical risks. Such holistic safety-scientific understanding of the COVID-19 crisis can furthermore be instrumental to be better prepared for a future pandemic.

negative: Developing an ultra-efficient microsatellite discoverer to find structural differences between SARS-CoV-1 and Covid-19 MOTIVATION: Recently, the outbreak of Coronavirus-Covid-19 has forced the World Health Organization to declare a pandemic status. A genome sequence is the core of this virus which interferes with the normal activities of its counterparts within humans. Analysis of its genome may provide clues toward the proper treatment of patients and the design of new drugs and vaccines. Microsatellites are composed of short genome subsequences which are successively repeated many times in the same direction. They are highly variable in terms of their building blocks, number of repeats, and their locations in the genome sequences. This mutability property has been the source of many diseases. Usually the host genome is analyzed to diagnose possible diseases in the victim. In this research, the focus is concentrated on the attacker's genome for discovery of its malicious properties. RESULTS: The focus of this research is the microsatellites of both SARS and Covid-19. An accurate and highly efficient computer method for identifying all microsatellites in the genome sequences is discovered and implemented, and it is used to find all microsatellites in the Coronavirus-Covid-19 and SARS2003. The Microsatellite discovery is based on an efficient indexing technique called K-Mer Hash Indexing. The method is called Fast Microsatellite Discovery (FMSD) and it is used for both SARS and Covid-19. A table composed of all microsatellites is reported. There are many differences between SARS and Covid-19, but there is an outstanding difference which requires further investigation. AVAILABILITY: FMSD is freely available at https://gitlab.com/FUM_HPCLab/fmsd_project, implemented in C on Linux-Ubuntu system. Software related contact: hossein_savari@mail.um.ac.ir.

negative: Persistence of lymphocytopenia with CT abnormalities among patients with critical H7N9 swine-origin influenza A virus infection PURPOSE: H7N9 is an emerging pathogen with associated morbidity and mortality, and a broader understanding of the chest radiographic characteristics associated with human H7N9 infections is needed. This study was performed to determine the time course of recovery from lymphocytopenia and resolution of pneumonitis of critical H7N9 infection patients. MATERIALS AND METHODS: We performed chest X-ray and computed tomography (CT) for patients with H7N9 influenza. Lesion patterns, distributions, and changes at follow-up chest X-ray and/or CT were investigated. The time to progression on chest CT image, and the time to resolution of the chest CT findings were assessed. RESULTS: Lymphocytopenia was a common laboratory test abnormality. The most common CT findings were lobar consolidation with air bronchogram and ground-glass opacities. For 7 recovering patients, the time to resolution of the chest CT findings was 10–90 days. Fibrosis and traction bronchiectasis were the main features on the CT scans of recovering patients. Interestingly, the time to recovery from lymphopenia was highly consistent with time to resolution of the chest CT findings. CONCLUSIONS: We have shown the presence of radiographic abnormalities among H7N9 patients. Monitoring of the variation of lymphocytes for H7N9 patients has important clinical significance, especially for prediction of the resolution of pneumonitis.

negative: Novel Coronavirus Disease (COVID-19) The present outbreak of the novel coronavirus initially called as “2019 novel coronavirus” or “2019-nCoV” by the World Health Organization (WHO), is also known as “Wuhan coronavirus” or “Wuhan pneumonia”, as it started in the Wuhan city of China in early December of 2019. This new coronavirus-associated acute respiratory deadly disease is now officially named as Corona Virus Disease-19 (COVID-19) by the WHO. From China, this epidemic has now spread to all over the world. On 11 March 2020, the WHO recognised COVID-19 as a pandemic. A pandemic refers to a disease that has spread to several countries, continents, if not worldwide. While the information available on this newly identified virus is limited and evolving, here is a quick run-down of what has been figured out so far.

negative: Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS) Abstract The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared as global public health emergency by WHO on Jan 30, 2020. Despite massive efforts from various governmental, health and medical organizations, the disease continues to spread globally with increasing fatality rates. Several experimental drugs have been approved by FDA with unknown efficacy and potential adverse effects. The exponentially spreading pandemic of COVID-19 deserves prime public health attention to evaluate yet unexplored arenas of management. We opine that one of these treatment options is low dose radiation therapy for severe and most critical cases. There is evidence in literature that low dose radiation induces an anti-inflammatory phenotype that can potentially afford therapeutic benefit against COVID-19- related complications that are associated with significant morbidity and mortality. Herein, we review the effects and putative mechanisms of low dose radiation that may be viable, useful and of value in counter-acting the acute inflammatory state induced by critical stage COVID-19.

negative: Clinical Characteristics of Coronavirus Pneumonia 2019 (COVID-19): An Updated Systematic Review OBJECTIVE Clinical characteristics of novel coronavirus pneumonia (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic. METHODS Systematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed. RESULTS Seventy-two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p<0.001). INTERPRETATION This large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies.

negative: Psychotherapy in the Post-COVID-19 Era This column anticipates challenges likely to be faced by psychotherapists and their patients after the coronavirus disease 2019 (COVID-19) pandemic subsides. It looks beyond the current impact of loneliness, isolation, thwarted belongingness, and loss toward the longer term impact of moral injury and blocked opportunities for mourning.

negative: Posttraumatic stress disorder and depression of survivors 12 months after the outbreak of Middle East respiratory syndrome in South Korea BACKGROUND: The 2015 outbreak of Middle East Respiratory Syndrome (MERS) in the Republic of Korea is a recent and representative occurrence of nationwide outbreaks of Emerging Infectious Diseases (EIDs). In addition to physical symptoms, posttraumatic stress disorder (PTSD) and depression are common following outbreaks of EID. METHODS: The present study investigated the long-term mental health outcomes and related risk factors in survivors of MERS. A prospective nationwide cohort study was conducted 12 months after the MERS outbreak at multi-centers throughout Korea. PTSD and depression as the main mental health outcomes were assessed with the Impact of Event Scale-Revised Korean version (IES-R-K) and the Patient Health Questionnaire-9 (PHQ-9) respectively. RESULTS: 42.9% of survivors reported PTSD (IES-R-K ≥ 25) and 27.0% reported depression (PHQ-9 ≥ 10) at 12 months post-MERS. A multivariate analysis revealed that anxiety (adjusted odds ratio [aOR], 5.76; 95%CI, 1.29-25.58; P = 0.021), and a greater recognition of stigma (aOR, 11.09, 95%CI, 2.28-53.90; P = 0.003) during the MERS-affected period were independent predictors of PTSD at 12 months after the MERS outbreak. Having a family member who died from MERS predicted the development of depression (aOR, 12.08, 95%CI, 1.47-99.19; P = 0.020). CONCLUSION: This finding implies that psychosocial factors, particularly during the outbreak phase, influenced the mental health of patients over a long-term period. Mental health support among the infected subjects and efforts to reduce stigma may improve recovery from psychological distress in an EID outbreak.

negative: Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-05965-1) contains supplementary material, which is available to authorized users.

negative: Recent advances in the understanding and management of cystic fibrosis pulmonary exacerbations Pulmonary exacerbations are common events in cystic fibrosis and have a profound impact on quality of life, morbidity, and mortality. Pulmonary exacerbation outcomes remain poor and a significant proportion of patients fail to recover their baseline lung function despite receiving aggressive treatment with intravenous antibiotics. This focused review provides an update on some of the recent advances that have taken place in our understanding of the epidemiology, pathophysiology, diagnosis, and management of pulmonary exacerbations in cystic fibrosis as well as direction for future study.

negative: COVID-19 and addiction BACKGROUND AND AIMS: 2019-coronavirus disease (COVID-19) is causing insurmountable psychosocial impact on the whole mankind. Marginalized community, particularly those with substance use disorders (SUD), are particularly vulnerable to contract the infection and also likely to suffer from greater psychosocial burden. This article analyses the intricate bi-directional relationship between COVID-19 and addiction. METHODS: Pubmed and Google Scholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Addiction”, “Opioid”, “Alcohol”, “Smoking”, “Addiction Psychiatry”, “Deaddiction”, “Substance use disorders”, “Behavioral addiction”. Few newspaper reports related to COVID-19 and addiction have also been added as per context. RESULTS: People with SUD are at greater risk of worse COVID-19 outcome. There is surge of addictive behaviors (both new and relapse) including behavioral addiction in this period. Withdrawal emergencies and death are also being increasingly reported. Addicted people are especially facing difficulties in accessing the healthcare services which are making them prone to procure drugs in illegal means. CONCLUSION: COVID-19 and addiction are the two pandemics which are on the verge of collision causing major public health threat. While every effort must be taken to make the public aware of deleterious effects of SUD on COVID-19 prognosis, the resumption of deaddiction services and easier accessibility of prescription drugs are needs of the hour.

negative: SARS-CoV-2, COVID-19 and inherited arrhythmia syndromes Abstract Ever since the first case was reported at the end of 2019, the SARS-COV-2 virus and associated lung disease COVID-19 has spread throughout the world and has become a pandemic. In particular, the high transmission rate of the virus has made it a threat to public health globally. Currently, there is no proven effective therapy against the virus, and the impact on other diseases is also uncertain, especially inherited arrhythmia syndrome. Arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome. This may be of importance for patients with an increased risk for cardiac arrhythmias, either secondary to acquired conditions or co-morbidities or consequent to inherited syndromes. Management of patients with inherited arrhythmia syndromes such as Long QT syndrome, Brugada syndrome, Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging. Depending on the inherited defect involved, these patients may be susceptible to pro-arrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances and use of antiviral drugs. We here describe the potential COVID-19 associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic.

negative: Identification of heat-dissociable RNA complexes in two porcine coronaviruses THE coronavirus genome has been shown to comprise single-stranded RNA(1,2). Examination of the viral nucleic acid synthesised by pig kidney cells infected with transmissible gastroenteritis virus (TGEV) suggested that several molecular species, ranging in size between 18 and 28S, were involved in the viral replicative cycle(3); similarly Tannock found a wide variation in the size of RNA molecules extracted from avian infectious bronchitis virus (IBV) by a phenol–sodium dodecyl sulphate (SDS) method(2). Extraction of IBV RNA by 1% SDS at 60 °C has, however, revealed a single component of molecular weight 9×10(6) corresponding to 60S by electrophoresis through 2.2% polyacrylamide gels(4).

negative: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.

negative: Acute respiratory failure in COVID-19: is it “typical” ARDS? In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8–12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality.

negative: Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19 We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.

negative: Perspectives on the death investigation during the COVID-19 pandemic Abstract The pandemic of COVID-19 caused by 2019-nCoV outbreaks in most of the countries, which has subsequently spread rapidly and become a pandemic worldwide. Due to the strong infectivity of COVID-19 and lack of experience of performing an autopsy to infectious disease-induced death, the pandemic created some challenges for forensic practitioners. In this article, we summarize the experience of how we handle the confirmed or suspected infectious cases, and give some perspectives for the future.

negative: SARS: prognosis, outcome and sequelae Severe acute respiratory syndrome (SARS) is associated with considerable morbidity and mortality in the acute phase. Worldwide case fatality rate is 11% (range 7 to 27%) for the most severely affected regions. Several adverse prognostic factors have been identified, including advanced age, presence of comorbidity, higher lactose dehydrogenase levels and initial neutrophil count, but the impact of viral and other host factors on outcome is unknown. Published data on sequelae of SARS are limited. Clinical follow‐up of patients who recovered from SARS has demonstrated radiological, functional and psychological abnormalities of varying degrees. In the early rehabilitation phase, many complained of limitations in physical function from general weakness and/or shortness of breath. In a small series of subjects who underwent CT scan of the chest, over half showed some patchy changes consistent with pulmonary fibrosis. Lung function testing at 6–8 weeks after hospital discharge showed mild or moderate restrictive pattern consistent with muscle weakness in 6–20% of subjects. Mild decrease in carbon monoxide diffusing capacity was detected in a minority of subjects. Preliminary evidence suggests that these lung function abnormalities will improve over time. Psychobehavioural problems of anxiety and/or depression were not uncommon in the early recovery phase, and improved over time in the majority of patients. Avascular necrosis of the hip has been reported as another complication. The long‐term sequelae of SARS are still largely unknown. It is important to follow up these patients to detect and appropriately manage any persistent or emerging long‐term sequelae in the physical, psychological and social domains.

negative: Cuidado respiratorio en COVID-19 Resumen Antecedentes El COVID-19 forma parte de la familia de los virus conocida como Coronaviridae. El nuevo patógeno β-coronavirus del subgénero Sarbecovirus se denominó inicialmente como el nuevo coronavirus (2019-nCoV); fue identificado en un brote de neumonía en Wuhan. Los pacientes desarrollan alteraciones en el sistema respiratorio, pudiendo llegar a padecer neumonía severa, edema pulmonar o síndrome de dificultad respiratoria aguda. Objetivo Revisar la evidencia científica disponible relacionada con el cuidado del sistema respiratorio, estableciendo pautas generales de tratamiento. Métodos Revisión narrativa de la literatura. Se realizó una búsqueda, selección y revisión de artículos originales y secundarios escritos en inglés o español, en las diferentes bases de datos: NCBI, CENTRAL, MEDLINE y EMBASE, publicados hasta marzo del 2020. Resultados No se ha definido un tratamiento específico ante la nueva enfermedad, teniendo como principal medida terapéutica el control sintomático. Se recomienda utilizar elementos de bioseguridad: gafas, gorros, guantes, bata larga impermeable, tapabocas de alta eficiencia en personal sanitario (FFP2 o N95). En el paciente sintomático, utilizar tapabocas quirúrgico, jabón hospitalario, toallas de papel y alcohol al 70% o isopropílico. Utilizar oxígeno mediante sistemas de bajo flujo. En ventilación mecánica, programar modos VCP o VCV, Vt 4-6ml/kg, Fr≤35, FiO2 para PaO2 de 60mmHg o SpO2 de 92-96%, PEEP 12-17cmH2O, ventilación prono si PAFI≤150 con una relación 16/8 o 18/6, óxido nítrico 5-20ppm. Conclusiones Usar equipos de bioseguridad con el fin de interrumpir la transmisión. En hipoxemia, utilizar sistemas de oxigenoterapia a bajo flujo. Usar estrategias de protección pulmonar, disminución de volúmenes corrientes, presiones de meseta y frecuencias respiratorias, implementación de valores de PEEP elevados, bajos valores de presión de conducción y ventilación en prono, los cuales han demostrado mejoraría en la hipoxemia y la sobrevida en pacientes con síndrome de dificultad respiratoria aguda. Abstract Background COVID-19 is part of the family of viruses known as Coronaviridae. The new pathogen β-coronavirus of the subgenus Sarbecovirus was initially named as a novel coronavirus (2019-nCoV), identified in a pneumonia outbreak in Wuhan. Patients developed alterations in the respiratory system leading to severe pneumonia, pulmonary oedema, and acute respiratory distress syndrome. Objective To review the available scientific evidence related to the care of the respiratory system in order to establish general treatment guidelines. Methods Narrative review of the literature was carried out that included a search, selection, and review of original and secondary articles written in English or Spanish in the different databases: NCBI, CENTRAL, MEDLINE and EMBASE published up to March 2020. Results No specific treatment for the new disease has been defined, with symptomatic control as the main therapeutic measure. The use of biosecurity elements, such as goggles, hats, gloves, long waterproof aprons, high efficiency masks for healthcare personnel (FFP2 or N95) is recommended. In symptomatic patients use surgical masks, hospital soap, paper towels, and 70% alcohol or isopropyl alcohol. Use oxygen through low flow systems. A mechanical ventilation program in VCP or VCV modes, Vt 4-6ml/Kg, Fr≤35, FiO2 for PaO2 =60mmHg or SpO2 92-96%, PEEP 12-17cmH2O, prone ventilation if PAFI≤150 with ratio 16/8 or 18/6, nitric oxide 5-20ppm. Conclusions Use biosecurity equipment in order to prevent transmission. In hypoxaemia use low flow oxygen therapy systems. Use lung protection strategies, decrease in tidal volumes, plateau pressures and respiratory rates, plus implementation of high PEEP values, low conduction pressure values and prone ventilation. These have been shown to improve hypoxaemia and survival in patients with acute respiratory distress syndrome.

negative: Global dynamics of a SUIR model with predicting COVID-19 Since December 2019, A novel coronavirus (2019-nCoV) has been breaking out in China, which can cause respiratory diseases and severe pneumonia. Epidemic models relying on the incidence rate of new cases for forecasting epidemic outbreaks have received increasing attention. However, many prior works in this area mostly focus on the application of the traditional SIR model and disregard the transmission characteristics of 2019-nCoV, exceptionally the infectious of undiagnosed cases. Here, we propose a SUIR model based on the classical SIR model object to supervise the effective prediction, prevention, and control of infectious diseases. SUIR model adds a unique $U$ (Undiagnosed) state of the epidemic and divides the population into four states: S (Susceptible), U (Undiagnosed), I (Infectious and Uninfectious), and R (Recovered). This approach enables us to predict the incidence of 2019-nCoV effectively and the clear advantage of the model accuracy more reliable than the traditional SIR model.

negative: Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis. OBJECTIVE. The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia. MATERIALS AND METHODS. We reviewed the clinical data and CT examinations of 15 consecutive pregnant women with COVID-19 pneumonia in our hospital from January 20, 2020, to February 10, 2020. A semiquantitative CT scoring system was used to estimate pulmonary involvement and the time course of changes on chest CT. Symptoms and laboratory results were analyzed, treatment experiences were summarized, and clinical outcomes were tracked. RESULTS. Eleven patients had successful delivery (10 cesarean deliveries and one vaginal delivery) during the study period, and four patients were still pregnant (three in the second trimester and one in the third trimester) at the end of the study period. No cases of neonatal asphyxia, neonatal death, stillbirth, or abortion were reported. The most common early finding on chest CT was ground-glass opacity (GGO). With disease progression, crazy paving pattern and consolidations were seen on CT. The abnormalities showed absorptive changes at the end of the study period for all patients. The most common onset symptoms of COVID-19 pneumonia in pregnant women were fever (13/15 patients) and cough (9/15 patients). The most common abnormal laboratory finding was lymphocytopenia (12/15 patients). CT images obtained before and after delivery showed no signs of pneumonia aggravation after delivery. The four patients who were still pregnant at the end of the study period were not treated with antiviral drugs but had achieved good recovery. CONCLUSION. Pregnancy and childbirth did not aggravate the course of symptoms or CT features of COVID-19 pneumonia. All the cases of COVID-19 pneumonia in the pregnant women in our study were the mild type. All the women in this study-some of whom did not receive antiviral drugs-achieved good recovery from COVID-19 pneumonia.

negative: Pregnancy and breastfeeding during COVID-19 pandemic: A systematic review of published pregnancy cases Background: The COVID-19 pandemic is an emerging concern regarding the potential adverse effects during pregnancy. This study reviews knowledge on the impact of COVID-19 on pregnancy and describes the outcome of published cases of pregnant women diagnosed with COVID-19, as well as the characteristics of COVID-19 positive women who delivered in Portugal by 31 of March 2020. Methods: Searches were conducted in PubMed up to 8 April 2020, using PRISMA standards, to identify original published studies describing pregnant women at any gestational age diagnosed COVID-19. There were no date or language restrictions on the search. All identified studies were included irrespective of assumptions on study quality. Portuguese cases were ascertained by contact with all Portuguese maternities and based on the information provided by their health professionals. Results: We identified 30 original studies reporting 212 cases of pregnant women with COVID-19 (30 discharged while pregnant), 200 from China and 12 from other countries. The 182 published deliveries resulted in one stillbirth and 185 live births. Four women with severe COVID-19 required admission to an intensive care unit but no cases of maternal death were reported. There was one neonatal death. Preterm births occurred in 28.7% of cases, but it is unclear whether this was iatrogenic. All cases with amniotic fluid, placenta, and/or cord blood analyzed for the SARS-CoV-2 virus were negative. Four newborns were positive for SARS-CoV-2 and three newborns had high levels of IgM antibodies. None of the first eight infants born in Portugal tested positive. Breast milk samples from 13 mothers and described in seven studies showed no evidence of SARS-CoV-2. Conclusion: The evidence related to the effect of COVID-19 on pregnant women is still limited. Pregnant women and newborns should be considered particularly vulnerable populations regarding COVID-19 prevention and management strategies.

negative: Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division. The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells.

negative: Laparoscopic surgical treatment of ileocecal Crohn's disease: Impact of obesity on short term results. INTRODUCTION The aim of our study was to analyse the short-term outcomes of laparoscopic surgery for a no medical responding ileocolic Cohn's disease in a single centre according to the presence of obesity. METHODS A cross-sectional study was performed including all consecutive patients who underwent laparoscopic resection for ileocecal Crohn's disease from November 2006 to November 2015. Patients were divided according to body mass index ≥ 30 kg/m2 in order to study influence of obesity in the short-term outcomes. The following variables were studied: characteristics of patients, surgical technique and postoperative results (complications, reintervention, readmission and mortality) during first 30 postoperative days. RESULTS A total of 100 patients were included (42 males) with a mean age of 39.7±15.2 years (range 18-83). The overall complication rate was 20% and only 3 patients had an anastomotic leak. Seven patients needed reoperation in the first 30 days postop (7%). The median postoperative length of hospitalization was 5.0 days. Operative time was significantly longer in patients with obesity (130 vs. 165minutes, P=.007) but there were no significant differences among the postoperative results in patients with and without obesity. CONCLUSIONS This study confirmed that laparoscopic approach for ileocecal Cohn's disease is a safety and feasible technique in patients with obesity. In this last group of patients we only have to expect a longer operative time.

negative: Author Index to Volume 65, issues 1 and 2

negative: The impact of undetected cases on tracking epidemics: the case of COVID-19 One of the key indicators used in tracking the evolution of an infectious disease isthe reproduction number. This quantity is usually computed using the reportednumber of cases, but ignoring that many more individuals may be infected (e.g.asymptomatics). We propose a statistical procedure to quantify the impact of un-detected infectious cases on the determination of the effective reproduction number. Our approach is stochastic, data-driven and not relying on any compartmentalmodel. It is applied to the COVID-19 case in eight different countries and all Italianregions, showing that the effect of undetected cases leads to estimates of the effective reproduction numbers larger than those obtained only with the reported cases by factors ranging from two to ten. Our findings urge caution about deciding when and how to relax containment measures based on the value of the reproduction number.

negative: COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18–98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT.

negative: Guidelines for preventing respiratory illness in older adults aged 60 years and above living in long-term care: A rapid review of clinical practice guidelines Background: The overall objective of this rapid review was to identify infection protection and control recommendations from published clinical practice guidelines (CPGs) for adults aged 60 years and older in long-term care settings Methods: Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, and relevant CPG publishers/repositories were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AGREE-II) were carried out by single reviewers. Results: A total of 17 relevant CPGs were identified, published in the USA (n=8), Canada (n=6), Australia (n=2), and the United Kingdom (n=1). All of the CPGs dealt with infection control in long-term care facilities (LTCF) and addressed various types of viral respiratory infections (e.g., influenza, COVID-19, severe acute respiratory syndrome). Ten or more CPGs recommended the following infection control measures in LTCF: hand hygiene (n=13), wearing personal protective equipment (n=13), social distancing or isolation (n=13), disinfecting surfaces (n=12), droplet precautions (n=12), surveillance and evaluation (n=11), and using diagnostic testing to confirm illness (n=10). While only two or more CPGs recommended these infection control measures: policies and procedures for visitors, staff and/or residents (n=9), respiratory hygiene/cough etiquette (n=9), providing supplies (n=9), staff and/or residents education (n=8), increasing communication (n=6), consulting or notifying health professionals (n=6), appropriate ventilation practices (n=2), and cohorting equipment (n=2). Ten CPGs also addressed management of viral respiratory infections in LTCF and recommended antiviral chemoprophylaxis (n=10) and one CPG recommended early mobilization of residents. Conclusion: The recommendations from current guidelines overall seem to support environmental measures for infection prevention and antiviral chemoprophylaxis for infection management as the most appropriate first-line response to viral respiratory illness in long-term care.

negative: Clinical characteristics of IgG4-RD patients infected with COVID-19 in Hubei, China OBJECTIVE: IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ, chronic and progressive disease. Therefore, we conducted a study to investigate the susceptibility of COVID-19 in IgG4-RD patients in Hubei province, and to characterize the clinical manifestation of COVID-19 in IgG4-RD patients. METHODS: A follow-up system that includes over 200 IgG4-RD patients across the country during the past ten years. A total of ninety-one patients with IgG4-RD who live in Hubei, China were identified and responded to our survey. Medical history, clinical symptoms, laboratory tests, CT imaging, and treatment were obtained through a standardized data collection form, and then independently reviewed by two investigators. RESULTS: 2 of 91 cases were infected with COVID-19. Both of them were classified as moderate type. The symptoms such as fever and cough and radiologic features were similar to other COVID-19 patients. Neither of them episode recurrent of IgG4-RD nor progressed to severe or critical condition of COVID-19 under the condition of continuous oral low-dose of glucocorticoids. Besides, patient 2 took a long time for SARS-CoV-2 nucleic acid to turn negative. CONCLUSION: IgG4-RD patients may belongs to the susceptible population of COVID-19 infection, and thus need more careful personal protection. Early identification and properly treatment are very important to prevent IgG4-RD patients with COVID-19 from progression to severe condition.

negative: Chapter 7 Infections and multiple sclerosis Abstract Multiple sclerosis is a chronic inflammatory condition of unknown cause. Increasing evidence suggests that the disease develops as a result of interactions between the environment and the immune system in genetically susceptible individuals. It has long been recognized that infections may serve as environmental triggers for the disease, and a large number of pathogens have been proposed to be associated with multiple sclerosis. Here, we detail the historical basis linking infections to multiple sclerosis and review the epidemiology of the disease, which suggests a possible relationship with infectious agents. We also describe pathophysiologic studies in animals and other human demyelinating diseases that have demonstrated a variety of mechanisms by which infectious agents may induce chronic, relapsing central nervous system disease with myelin damage and relative preservation of axons, similar to multiple sclerosis. In addition, we discuss recent studies in individuals with multiple sclerosis indicating enhanced immune responses to infectious antigens, though not consistently demonstrating evidence for ongoing infection. Taken together, these studies suggest a role for infectious agents in the development of multiple sclerosis. Conclusive evidence, however, remains lacking.

negative: A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2 In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socio‐economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo‐embolic complications and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19‐related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.

negative: The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease Abstract Coronavirus disease 2019 (COVID-19), caused by a novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in a cluster of patients presenting with pneumonia symptoms in Wuhan, China, in December of 2019. Over the past few months, COVID-19 has developed into a worldwide pandemic, with over 400,000 documented cases globally as of March 24, 2020. The SARS-CoV-2 virus is most likely of zoonotic origin, but has been shown to have effective human-to-human transmission. COVID-19 results in mild symptoms in the majority of infected patients, but can cause severe lung injury, cardiac injury, and death. Given the novel nature of COVID-19, no established treatment beyond supportive care exists currently, but extensive public-health measures to reduce person-to-person transmission of COVID-19 have been implemented globally to curb the spread of disease, reduce the burden on healthcare systems, and protect vulnerable populations, including the elderly and those with underlying medical comorbidities. Since this is an emerging infectious disease, there is, as of yet, limited data on the effects of this infection on patients with cardiovascular disease, particularly so for those with congenital heart disease. We summarize herewith the early experience with COVID-19 and consider the potential applicability to and implications for patients with cardiovascular disease in general and congenital heart disease in particular.

negative: COVID-19 in a Long-Term Care Facility - King County, Washington, February 27-March 9, 2020 On February 28, 2020, a case of coronavirus disease (COVID-19) was identified in a woman resident of a long-term care skilled nursing facility (facility A) in King County, Washington.* Epidemiologic investigation of facility A identified 129 cases of COVID-19 associated with facility A, including 81 of the residents, 34 staff members, and 14 visitors; 23 persons died. Limitations in effective infection control and prevention and staff members working in multiple facilities contributed to intra- and interfacility spread. COVID-19 can spread rapidly in long-term residential care facilities, and persons with chronic underlying medical conditions are at greater risk for COVID-19-associated severe disease and death. Long-term care facilities should take proactive steps to protect the health of residents and preserve the health care workforce by identifying and excluding potentially infected staff members and visitors, ensuring early recognition of potentially infected patients, and implementing appropriate infection control measures.

negative: First case of bacteremia caused by Janibacter hoylei Janibacter hoylei has previously been isolated only from an air sample in the upper atmosphere and clinical significance of J. hoylei was not yet established. Herein, we report a case of bacteremia caused by J. hoylei. An 8‐week‐old previously healthy male infant presented to the emergency room with fever. Blood culture yielded growth of Gram‐positive bacilli and this microorganism could not be identified with conventional phenotypic methods. The isolate was identified by 16S rRNA gene sequencing, and the patient was successfully treated with vancomycin. To our knowledge, this is the first report of the recovery of J. hoylei in humans. This case shows that J. hoylei can be a potential pathogen in young children.

negative: COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-Cov-2, resulting in severe acute respiratory syndrome, with high potential of spreading and infecting humans worldwide. Since December 2019, when the virus was identified in humans, the literature on COVID-19 has grown exponentially and extrarespiratory symptoms including neurologic symptoms are increasingly highlighted. METHODS: Given the high and increasing number of publications reporting neurologic involvements of SARS-Cov-2, we thought that providing an update for neurologic complications of COVID-19 would be useful for physicians and especially young trainees in neurology and neurosurgery. Indeed, in this review we discuss several neurologic aspects reported in the literature to date including the evidence and pathways of neuroinvasion in COVID-19 and the main neurologic disorders reported in the literature to date, as well as future perspectives and the potential long-term consequence of current neuroinfection in COVID-19 patients. RESULTS: Currently, there is convincing evidence that SARS-CoV-2, the etiologic agent of COVID-19, can affect the nervous system, with damage and neurologic alterations. These neurologic disorders are grouped into several categories, ranging from nonspecific and moderate symptoms such as headache, myalgia, and hyposmia to severe symptoms including cerebrovascular disease and intracranial infections. Severe neurologic symptoms such as acute cerebrovascular disease occur only in a minority of patients with usual risk factors and are associated with poor outcome. However, most COVID-19 patients exhibit only minor or mild neurologic symptoms. CONCLUSIONS: Management of COVID-19 patients should include early clinical, radiologic, and laboratory neurologic assessment, with a close follow-up, especially in severe forms. Future studies should assess late and long-term consequences of current COVID-19 patients with neurologic involvement.

negative: Exploration on mechanism of anti-coronavirus of Sophora flavescens through multi-pathway/ 苦参多路径抗冠状病毒的机制探究 The coronavirus disease 2019 (COVID-19), originated in Wuhan city, Hubei Province, China in December 2019, and then quickly spread to most provinces and regions in China and even spread to many countries abroad. COVID-19 is characterized by wide epidemic, strong infectivity, rapid onset and critical condition. In the face of this epidemic, all parts of the country quickly set off a peak in the fight against COVID-19, but no effective drug for COVID-19 has been developed in the short term. Recently, many hospitals have combined traditional Chinese medicine with western medicine in treatment, and the clinical effect is remarkable, which proves the antiviral effect of traditional Chinese medicine. A large number of pharmacological and clinical studies have proved that the Chinese materia medica S. flavescens has significant antiviral effect. In this paper, the mechanism of anti-coronavirus effect of S. flavescens is expounded from multiple pathways, such as type I interferon, NF-κB signal pathway, ERK signal pathway, PI3K/Akt signal pathway and matrine alkaloids, etc. It is intended to provide reference for clinical treatment of coronavirus infection pneumonia and research and development of related drugs of S. flavescens.

negative: Convalescent plasma: A possible treatment protocol for COVID- 19 patients suffering from diabetes or underlying liver diseases BACKGROUND & AIM: As on date, no specific treatment is available for devastating COVID-19 (SARS-CoV-2) infection. This pandemic viral infection has affected over 200 countries within a very short time and created a calamitous situationacross the globe. As per WHO guidelines, the treatment is mainly symptomatic andsupportive. This clinical protocol has not proven sufficient to save the lives of COVID-19 patients suffering from diabetes or having underlying liver diseases; hence there isutmost need to tackle this situation by other means such as Convalescent Plasma (CP)therapy. METHODS: A comprehensive literature survey was carriedout using Elsevier, PubMed, Taylor & Francis, Springer, Nature and Google searchengines. RESULTS: The patients suffering from diabetes or liverdysfunction or any other underlying diseases are at greatest risk of SARS-CoV-2infection. From the study, it is proved that plasma collected from the recovered patientsof viral infection has considerable potential to treat the viral disease without theoccurrence of adverse effects. CONCLUSION: The CP therapy can bea possible life saving alternative to treat critical COVID-19 patients having diabetes orunderlying liver dysfunction. Hence, randomised clinical trials are recommended at theearliest to save the lives of infected individuals of COVID-19.

negative: COVID-19 pandemic: a stress test for interventional radiology

negative: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.

negative: Can we contain the COVID-19 outbreak with the same measures as for SARS? Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.

negative: Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002–2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.

negative: Prise en charge de 90 patients suspects de syndrome respiratoire aigu sévère. Expérience d'une collaboration épidémioclinique en situation d'alerte sanitaire liée à une infection émergente() OBJECTIVE: The characteristics of patients with a suspected SARS hospitalized in a Paris hospital were studied to analyze the hypothetic differences between epidemiologic and clinical teams in the management of an epidemic emerging disease, and to gather experience for the management of the next outbreak. STUDY DESIGN: All 90 patients hospitalized between March 16 and April 30, 2003, were included. Epidemiological and clinical data were shared with the French National Institute for Health. Cases were classified according to both the official definition (“possible”, “probable”, “excluded”) and a local one, adapted from the official definition but including an additional level of suspicion (“equivocal”), intermediate between “possible” and “excluded”. RESULTS: The initial assessment was different in 39% of the cases (n = 35), according to epidemiological (n = 24) or clinical (n = 11) elements. The final assessment diverged in 54% of the cases (n = 47). All patients were officially considered as "excluded" for epidemiologists, while 47 remained as "possible" or "equivocal" cases of SARS according to the clinicians. CONCLUSION: The risk assessment was different in almost 40% of the cases, with no impact on epidemic diffusion or hospital-borne exposure as no probable case of SARS was diagnosed among these patients or their households. The confrontation of these different but complementary points of view will thus enrich the interdisciplinary management of eventual future outbreaks.

negative: Abstracts from the 36th Annual Meeting of the Society of General Internal Medicine

negative: [Consecutive five-year follow-up analysis of specific IgG antibody of 22 cases of SARS patients after recovery]. To study IgG antibody persistence and temporal change in SARS coronavirus (SARS-CoV) infected patients, 22 patients recovered from SARS in Beijing were recruited and followed-up from 2004 to 2008, serum samples from patients were collected every year. We checked and analyzed the SARS-CoV IgG antibody (Ab) for five consecutive years using the commercial ELISA test kit. The results showed that: all of the serum were SARS-IgG antibody-positive the first year after recovery, the titer of most serum remained at high levels at the 2ed and 3rd year post infection. The Ab titers significantly declined at 4th year post infection. The IgG Ab was almost undetectable after 5 years post infection. In conclusion, SARS-CoV IgG Ab can be maintained for more than 3 years post infection, however, the titer of IgG Ab has declined markedly 4 years later. These data provide a useful reference for diagnosis and control of SARS infection, the evaluation of immune response and vaccine efficacy.

negative: Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS). BACKGROUND A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS). METHODS Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months. RESULTS Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients. CONCLUSIONS The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.

negative: Caring for Patients with Rectal Cancer During the COVID-19 Pandemic The extraordinary spread of the novel coronavirus (COVID-19) has dramatically and rapidly changed the way in which we provide medical care for patients with all diagnoses. Conservation of resources, social distancing, and the risk of poor outcomes in COVID-19-positive cancer patients have forced practitioners and surgeons to completely rethink routine care. The treatment of patients with rectal cancer requires both a multidisciplinary approach and a significant amount of resources. It is therefore imperative to rethink how rectal cancer treatment can be aligned with the current COVID-19 pandemic paradigms. In this review, we discuss evidence-based recommendations to optimize oncological outcomes during the COVID-19 pandemic.

negative: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival.

negative: Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.

negative: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.

negative: Isolation and characterization of a coronavirus from elk calves with diarrhea. This is the first report of the isolation of a coronavirus from elk calves. Two fecal samples from elk calves with diarrhea were shown to be positive for coronavirus-like particles by electron microscopy, and the particles were propagated in the human rectal tumor-18 cell line. After 24 h, syncytia were observed, and cell culture supernatants from both samples showed hemagglutinating activity with mouse erythrocytes. Cells infected with both elk coronavirus (ECV) isolates reacted with Z3A5, a monoclonal antibody against the spike protein of bovine coronavirus (BCV), on an indirect fluorescent antibody test. The protein profiles of both ECV isolates were similar to that of BCV as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. On Northern blot analysis, the transcriptional pattern of ECV was typical of coronaviruses, with a nested set of transcripts with common 3' end sequences. Based on a published nucleoprotein gene sequence for BCV (Mebus isolate), we arbitrarily designed two primers for amplification by PCR. After cloning, the nucleoprotein was sequenced and a high degree of homology (99%) between the nucleoprotein gene sequences of ECV and BCV was observed. Thus, ECV is closely related genetically and antigenically to BCV and will be a new member of antigenic group 2 of the mammalian coronaviruses, which possess hemagglutinin-esterase protein.

negative: Evaluating the different control policies for COVID-19 between mainland China and European countries by a mathematical model in the confirmed cases This study focuses on evaluating the different policies of controlling the outbreak of COVID-19 in mainland China and in some European countries. The study is based on mathematical model which is a modified susceptible-infected-recovered (SIR) model. The model takes death and recovery into consideration which in convenience is called the susceptible-infected-recovered-death (SIRD) model. The criterion for the recovered patients is assumed by COVID-19 nucleic acid testing negative. The mathematical model is constructed by retrospective study. Determination of the parameters in the model is based on the epidemic bulletin supplied by the Chinese Center for Disease Control and Prevention (CDC) and National Health Commission of the People's Republic of China (NHC) from Jan 16 2020 to Mar 5 2020. The data cover the date when the epidemic situation is reported and the data showed that the epidemic situation is almost under control in China. The mathematical model mainly simulates the active cases and the deaths during the outbreak of COVID-19. Then apply the mathematical model to simulate the epidemic situations in Italy and Spain, which are suffering the outbreak of COVID-19 in Europe. The determination of the parameters for the 2 European countries is based on the data supplied by Worldometers. By comparing the difference of the parameters based on the same mathematical model, it is possible to evaluate the different policies in different countries. It turns out that the relatively easing control policies might lead to rapid spread of the disease.

negative: How might the NHS protect the mental health of health-care workers after the COVID-19 crisis?

negative: Intraruminal administration of milk in the calf as a model for ruminal drinking: Morphological and enzymatical changes in the jejunal mucosa In order to develop a calf model for studying the syndrome of ruminal drinking (RD) in veal calves, three dual-fistulated calves were used to test the effect of intraruminal administration of milk replacer on the jejunal mucosa. Biopsies of the proximal jejunal mucosa were taken through a jejunal fistula and the mucosal morphology and the activities of two brush border enzymes, lactase and alkaline phosphatase, were determined. Means of villus length and brush border enzyme activities decreased during the period of intraruminal administration of milk. The hyperplastic villus atrophy in this model was similar to that found in chronic RD patients in previous studies. This could not be associated with isolation of pathogenic micro-organisms from the faeces and is probably the consequence of the intraruminal milk feeding procedure itself. Clinical recovery from the signs of RD occurred rapidly after intraruminal administration of milk ceased and was followed by restoration of villus length and brush border enzyme activities 3–4 weeks later.

negative: Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics What is COVID-19? Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. What are the goals of this investigation? This study explains the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths and suggests general lessons learned for a strategy to cope with future epidemics similar to COVID-19 to reduce viral infectivity and negative impacts in economic systems and society. What are the results of this study? The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. What is a socioeconomic strategy to prevent future epidemics similar to COVID-19? Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. This study must conclude that a strategy to prevent future epidemics similar to COVID 19 has also to be designed in environmental and sustainability science and not only in terms of biology.

negative: A survey of UK acute clinicians' knowledge of personal protective requirements for infectious diseases and chemical, biological, and radiological warfare agents

negative: [Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region]. Objective: To understand the clinical characteristics, change of liver function, influencing factors and prognosis in hospitalized patients with coronavirus disease-19 (COVID-19) combined with liver injury. Methods: The general conditions, biochemical indicators of liver, blood clotting mechanism, routine blood test, UGT1A1 * 28 gene polymorphism and other data of 40 cases with COVID-19 admitted to the isolation ward of Tangdu Hospital were retrospectively analyzed. The clinical characteristics, influencing factors and prognosis of liver injury in patients with liver injury group and those with normal liver function group were compared. The mean of two samples in univariate analysis was compared by t-test and analysis of variance. The counting data was measured by χ(2) tests. The non-normal distribution measurement data were described by the median, and the non-parametric test was used. Statistically significant influencing factors were used as the independent variables in univariate analysis. Multiple logistic regression analysis was used to analyze the main influencing factors of liver injury. Results: Of the 40 cases, 25 were male (62.5%) and 15 were female (37.5%), aged 22 to 83 (53.87 ± 15.84) years. Liver injury was occurred in 22 cases (55%) during the course of the disease. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level was initially increased (4.4 to 3.5 times of the normal value) along with decrease of albumin in the second week, and the difference was statistically significant (P < 0.001). Ten cases (43.5%) had highest abnormal total blood bilirubin (54.1 μmol/ L). There was no correlation between the increase in transaminase and the increase in total blood bilirubin (R = -0.006, P = 0.972). Three cases had prothrombin activity (PTA) of ≤ 50%, 10 cases had elevated FDP, and 13 cases had elevated D-dimer, all of whom were severe or critically ill. Liver function injury was more likely to occur in patients who used many types of drugs and large amounts of hormones (P = 0.002, P = 0.031), and there was no correlation with the TA6TA7 mutation in the UGT1A1 * 28 gene locus. Multiple regression analysis showed that the occurrence of liver injury was only related to critical illness. The liver function of all patients had recovered within one week after conventional liver protection treatment. Conclusion: COVID-19 combined with liver function injury may be due to the slight elevation of transaminase, mostly around the second week of the disease course. Severe patients have a higher proportion of liver injury, and critical type is an independent risk factor for liver injury.

negative: Dynamics and Control of Diseases in Networks with Community Structure The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies.

negative: Drug Resistance in Infectious Diseases: Modeling, Parameter Estimation and Numerical Simulation Infectious diseases are drawing our attention again. In recent years, we have been confronted with SARS, bird-flu, swine-flu and many other severe diseases. In addition, pathogens are getting resistant to drugs controlling them. In this paper we establish a new population dynamical system of infectious diseases including drug treatment. We take into account both sensitive and resistant parasites. The unknown model parameters are fitted based on a set of data for malaria from Cisse, Burkina Faso. The fitted model is used to investigate the influence of drug treatment on drug resistance. Based on these investigations, treatment strategies to reduce drug resistance can be elaborated.

negative: COVID-19 outbreak: less stethoscope, more ultrasound

negative: Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS BACKGROUND: During the acute phase of severe acute respiratory syndrome (SARS), mononuclear cells infiltration, alveolar cell desquamation and hyaline membrane formation have been described, together with dysregulation of plasma cytokine levels. Persistent high-resolution computed tomography (HRCT) abnormalities occur in SARS patients up to 40 days after recovery. METHODS: To determine further the time course of recovery of lung inflammation, we investigated the HRCT and inflammatory profiles, and coronavirus persistence in bronchoalveolar lavage fluid (BALF) of 12 patients at recovery at 60 and 90 days. RESULTS: At 60 days, compared to normal controls, SARS patients had increased cellularity of BALF with increased alveolar macrophages (AM) and CD8 cells. HRCT scores were increased and correlated with T-cell numbers and their subpopulations, and inversely with CD4/CD8 ratio. TNF-α, IL-6, IL-8, RANTES and MCP-1 levels were increased. Viral particles in AM were detected by electron microscopy in 7 of 12 SARS patients with high HRCT score. On day 90, HRCT scores improved significantly in 10 of 12 patients, with normalization of BALF cell counts in 6 of 12 patients with repeat bronchoscopy. Pulse steroid therapy and prolonged fever were two independent factors associated with delayed resolution of pneumonitis, in this non-randomized, retrospective analysis. CONCLUSION: Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.

negative: Racial Disparities in Bariatric Surgery Complications and Mortality Using the MBSAQIP Data Registry BACKGROUND: Racial disparities in postoperative complications have been demonstrated in bariatric surgery, yet the relationship of race to complication severity is unknown. STUDY DESIGN: Adult laparoscopic primary bariatric procedures were queried from the 2015 and 2016 MBSAQIP registry. Adjusted logistic and multinomial regressions were used to examine the relationships between race and 30-day complications categorized by the Clavien-Dindo grading system. RESULTS: A total of 212,970 patients were included in the regression analyses. For Black patients, readmissions were higher (OR = 1.39, p < 0.0001) and the odds of a Grade 1, 3, 4, or 5 complication were increased compared with White patients (OR = 1.21, p < 0.0001; OR = 1.21, p < 0.0001; OR = 1.22, p = 0.01; and OR = 1.43, p = 0.04) respectively. The odds of a Grade 3 complication for Hispanic patients were higher compared with White patients (OR = 1.59, p < 0.0001). CONCLUSION: Black patients have higher odds of readmission and multiple grades of complications (including death) compared with White patients. Hispanic patients have higher odds of a Grade 3 complication compared with White patients. No significant differences were found with other races. Specific causes of these disparities are beyond the limitations of the dataset and stand as a topic for future inquiry.

negative: Optimal control of the COVID-19 pandemic with non-pharmaceutical interventions The COVID-19 pandemic has forced societies across the world to resort to social distancing to slow the spread of the SARS-CoV-2 virus. Due to the economic impacts of social distancing, there is growing desire to relax these measures. To characterize a range of possible strategies for control and to understand their consequences, we performed an optimal control analysis of a mathematical model of SARS-CoV-2 transmission. Given that the pandemic is already underway and controls have already been initiated, we calibrated our model to data from the US and focused our analysis on optimal controls from May 2020 through December 2021. We found that a major factor that differentiates strategies that prioritize lives saved versus reduced time under control is how quickly control is relaxed once social distancing restrictions expire in May 2020. Strategies that maintain control at a high level until summer 2020 allow for tapering of control thereafter and minimal deaths, whereas strategies that relax control in the short term lead to fewer options for control later and a higher likelihood of exceeding hospital capacity. Our results also highlight that the potential scope for controlling COVID-19 until a vaccine is available depends on epidemiological parameters about which there is still considerable uncertainty, including the basic reproduction number and the effectiveness of social distancing. In light of those uncertainties, our results do not constitute a quantitative forecast and instead provide a qualitative portrayal of possible outcomes from alternative approaches to control.

negative: Testing Case Number of Coronavirus Disease 2019 in China with Newcomb-Benford Law The coronavirus disease 2019 bursted out about two months ago in Wuhan has caused the death of more than a thousand people. China is fighting hard against the epidemics with the helps from all over the world. On the other hand, there appear to be doubts on the reported case number. In this article, we propose a test of the reported case number of coronavirus disease 2019 in China with Newcomb-Benford law. We find a $p$-value of $92.8\%$ in favour that the cumulative case numbers abide by the Newcomb-Benford law. Even though the reported case number can be lower than the real number of affected people due to various reasons, this test does not seem to indicate the detection of frauds.

negative: Burden and prevalence of prognostic factors for severe covid-19 disease in Sweden Objectives: Describe the burden and prevalence of prognostic factors of severe COVID-19 disease at national and county level in Sweden. Design: Cross sectional study Setting: Sweden Participants: 9,624,428 individuals living in Sweden on 31st December 2014 and alive on 1st January 2016 Main outcome measures: Burden and prevalence of prognostic factors for severe COVID-19 based on the guidelines from the World Health Organization and European Centre for Disease Prevention and Control, which are age 70 years and older, cardiovascular disease, cancer, chronic obstructive pulmonary disease, severe asthma, and diabetes. Prognostic factors were identified based on records for three years before 1st January 2016 from the Swedish National Inpatient and Outpatient Specialist Care Register, Prescribed Drug Register, and Cancer Register. Results: 22.1% of the study population had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions in the whole study population ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). Conclusions: The prevalence of prognostic factors for severe COVID-19 disease will aid authorities in optimally planning healthcare resources during the ongoing pandemic. Results can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning. This information is crucial when deciding appropriate strategies to mitigate the pandemic and reduce both the direct mortality burden from the disease itself, and the indirect mortality burden from potentially overwhelmed health systems.

negative: An Analytical Perspective on Pandemic Recovery After implementing restrictions to curb the spread of coronavirus, governments in the United States and around the world are trying to identify the path to social and economic recovery. The White House and the Centers for Disease Control and Prevention have published guidelines to assist US states, counties, and territories in planning these efforts. As the impact of the coronavirus pandemic has not been uniform, these central guidelines need to be translated into practice in ways that recognize variation among jurisdictions. We present a core methodology to assist governments in this task, presenting a case for appropriate actions at each stage of recovery based on scientific data and analysis. Specifically, 3 types of data are needed: data on the spread of disease should be analyzed alongside data on the overall health of the population and data on infrastructure-for example, the capacity of health systems. Local circumstances will produce different needs and present different setbacks, and governments may need to reinstate as well as relax restrictions. Transparent, defensible analysis can assist in making these decisions and communicating them to the public. In the absence of a widely administered vaccine, analysis remains one of our most important tools in addressing the coronavirus pandemic.

negative: The COVID-19 Pandemic and Physical Activity Abstract The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune, respiratory, cardiovascular, musculoskeletal systems and the brain. The cellular mechanisms and danger of this “second wave” effect of COVID-19 to the human body, along with the effects of aging, proper nutrition, and regular physical activity, are reviewed in this editorial article.

negative: Mapping the Landscape of Artificial Intelligence Applications against COVID-19 COVID-19, the disease caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization, with over 2.5 million confirmed cases as of April 23, 2020. In this review, we present an overview of recent studies using Machine Learning and, more broadly, Artificial Intelligence, to tackle many aspects of the COVID-19 crisis at different scales including molecular, clinical, and societal applications. We also review datasets, tools, and resources needed to facilitate AI research. Finally, we discuss strategic considerations related to the operational implementation of projects, multidisciplinary partnerships, and open science. We highlight the need for international cooperation to maximize the potential of AI in this and future pandemics.

negative: North American COVID-19 ST-segment elevation myocardial infarction (NACMI) registry: Rationale, design, and implications() BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that causes coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. Patients with cardiovascular risk factors or established cardiovascular disease are more likely to experience severe or critical COVID-19 illness and myocardial injury is a key extra-pulmonary manifestation. These patients frequently present with ST-elevation on an electrocardiogram (ECG) due to multiple etiologies including obstructive, non-obstructive, and/or angiographically normal coronary arteries. The incidence of ST-elevation myocardial infarction (STEMI) mimics in COVID-19 positive hospitalized patients, and the association with morbidity and mortality is unknown. Understanding the natural history and appropriate management of COVID-19 patients presenting with ST elevation is essential to inform patient management decisions and protect healthcare workers. METHODS: The Society for Cardiovascular Angiography and Interventions (SCAI) and The Canadian Association of Interventional Cardiology (CAIC) in conjunction with the American College of Cardiology Interventional Council have collaborated to create a multi-center observational registry, North American COVID-19 ST-Segment Elevation Myocardial Infarction (NACMI). This registry will enroll confirmed COVID-19 patients and persons under investigation (PUI) with new ST-segment elevation or new onset left bundle branch block (LBBB) on the ECG with clinical suspicion of myocardial ischemia. We will compare demographics, clinical findings, outcomes and management of these patients with a historical control group of over 15,000 consecutive STEMI activation patients from the Midwest STEMI Consortium using propensity matching. The primary clinical outcome will be in- hospital major adverse cardiovascular events (MACE) defined as composite of all-cause mortality, stroke, recurrent MI, and repeat unplanned revascularization in COVID-19 confirmed or PUI. Secondary outcomes will include the following: reporting of etiologies of ST Elevation; cardiovascular mortality due to myocardial infarction, cardiac arrest and /or shock; individual components of the primary outcome; composite primary outcome at one year; as well as ECG and angiographic characteristics. CONCLUSION: The multicenter NACMI registry will collect data regarding ST elevation on ECG in COVID-19 patients to determine the etiology and associated clinical outcomes. The collaboration and speed with which this registry has been created, refined, and promoted serves as a template for future research endeavors.

negative: COVID-19 Financial Resources for Physicians Abstract The appropriate focus in dealing with the COVID-19 pandemic in the United States has been addressing access and delivery of care to the population impacted by the outbreak. All sectors of the U.S economy have been significantly impacted including physicians. Physician groups of all specialties and sizes have experienced the financial impact of the pandemic. Hospitals have received billions of dollars to support and enable them to handle emergencies and cover the cost of the disruption. However, many Vascular Surgeons are under great financial pressure because of postponement of all non-emergency procedures. The Federal Government has announced a myriad of programs in the form of grants and loans to reimburse physicians for some expenses and loss of revenue. It is more than likely that unless the public health emergency subsides significantly, many practices will suffer dire consequences without additional financial assistance. We attempt to provide a concise listing of such programs and resources available to assist Vascular Surgeons who are small businesses in accessing these opportunities.

negative: Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

negative: Dos terapias conocidas podrían ser efectivas como adyuvantes en el paciente crítico infectado por COVID-19 Resumen La neumonía causada por coronavirus, que se originó en Wuhan, China, a finales de 2019, se ha extendido por todo el mundo convirtiéndose en una pandemia. Desafortunadamente, a día de hoy no existe ninguna vacuna específica para el virus COVID-19, y el tratamiento está siendo de soporte con añadido de antivirales y otros fármacos, sin que hasta la fecha se haya evidenciado un beneficio claro. Muchos de estos pacientes se deterioran rápidamente y requieren ser intubados y ventilados mecánicamente, lo que está provocando el colapso del sistema sanitario en muchos países debido a la falta de ventiladores y de camas de críticos. En este documento revisamos dos terapias adyuvantes sencillas de aplicar, sin efectos deletéreos y de un coste bajo que podrían ser de utilidad para el tratamiento de la infección por coronavirus agudo severo asociado al síndrome respiratorio agudo (SARS-CoV-2). La vitaminaC, un potente antioxidante, se ha convertido en una terapia relevante debido a sus beneficios potenciales cuando se administra por vía intravenosa. El efecto potencial de la vitaminaC en la reducción de la inflamación en los pulmones podría desempeñar un papel clave en la lesión pulmonar causada por la infección por coronavirus. Otra posible terapia eficaz es el ozono. Pese a la controversia que siempre le ha acompañado, se ha estudiado y utilizado ampliamente durante muchos años y su eficacia se ha demostrado en múltiples estudios. Sin embargo, nuestro objetivo no es hacer una revisión exhaustiva de dichas terapias sino difundir sus efectos beneficiosos. Obviamente, los ensayos clínicos son necesarios, pero dado el potencial beneficio de estas terapias, recomendamos incorporarlas al arsenal terapéutico para el tratamiento del SARS-CoV-2. Abstract Pneumonia caused by coronavirus, which originated in Wuhan, China, in late 2019, has been spread around the world already becoming a pandemic. Unfortunately, there is not yet a specific vaccine or effective antiviral drug for treating COVID-19. Many of these patients deteriorate rapidly and require intubation and are mechanically ventilated, which is causing the collapse of the health system in many countries due to lack of ventilators and intensive care beds. In this document we review two simple adjuvant therapies to administer, without side effects, and low cost that could be useful for the treatment of acute severe coronavirus infection associated with acute respiratory syndrome (SARS-CoV-2). VitaminC, a potent antioxidant, has emerged as a relevant therapy due to its potential benefits when administered intravenous. The potential effect of vitaminC in reducing inflammation in the lungs could play a key role in lung injury caused by coronavirus infection. Another potential effective therapy is ozone: it has been extensively studied and used for many years and its effectiveness has been demonstrated so far in multiples studies. Nevertheless, our goal is not to make an exhaustive review of these therapies but spread the beneficial effects themselves. Obviously clinical trials are necessaries, but due to the potential benefit of these two therapies we highly recommended to add to the therapeutic arsenal.

negative: Unprecedented disruptions of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak We assess the health and wellbeing of normal adults living and working after one month of confinement to contain the COVID-19 outbreak in China. On Feb 20 and 21, 2020, we surveyed 369 adults in 64 cities in China that varied in their rates of confirmed coronavirus cases on their health conditions, distress and life satisfaction. 27% of the participants worked at the office, 38% resorted to working from home, and 25% stopped working due to the outbreak. Those who stopped working reported worse mental and physical health conditions as well as distress. The severity of COVID-19 in a location predicts life satisfaction, and this relationship is contingent upon the existing chronic health issues and hours of exercise of the individuals. Our evidence supports the need to pay attention to the health of people who were not affected by the virus epidemiologically, especially for people who stopped working during the outbreak. Our results highlight that physically active people might be more susceptible to wellbeing issues during the lockdown. Policymakers who are considering introducing restrictive measures to contain COVID-19 may benefit from understanding such health and wellbeing implications.

negative: Informed public against false rumor in the social media era: Focusing on social media dependency Abstract This study explores how the public’s belief in false rumors about Middle East Respiratory Syndrome that spread across South Korea related to their accuracy-oriented information seeking as well as the moderating effects of people’s reasons for using social networking services (SNS). The survey results show that perceived credibility of false rumors did not affect accuracy-oriented information seeking. However, a significant result was shown in the moderating effect, such that SNS informational dependency interacted with false rumor credibility on accuracy-oriented information seeking. Overall, this study specifically identifies and discusses differences in SNS dependency and accuracy-oriented information seeking in the context of rumor communication to examine the construction of an informed public. Theoretical contributions of this study are discussed.

negative: Sunlight exposure increased Covid-19 recovery rates: A study in the central pandemic area of Indonesia Abstract This study aims to present the correlation between sunlight exposure and Covid-19 statuses in Jakarta, Indonesia. The secondary data analysis was derived from surveillance data for Covid-19 from government authorities, including the Ministry of Health, the Meteorological, Climatological, and Geophysical Agency, and the local government of Jakarta. Three statuses related to Covid-19 were examined in the study: incidence, death, and recovered. Meanwhile, sunlight exposure was presented as daily duration of it. Only the number of recovered patients correlated significantly with sunlight exposure (p-value = .025; r = 0.350). This study's findings showed that sunlight exposure was associated with recovery from Covid-19.

negative: Covid-19—The real role of NSAIDs in Italy

negative: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review BACKGROUND: The coronavirus disease (COVID-19) has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. As of 31 January 2020, this epidemic had spread to 19 countries with 11 791 confirmed cases, including 213 deaths. The World Health Organization has declared it a Public Health Emergency of International Concern. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O’Malley. In this scoping review, 65 research articles published before 31 January 2020 were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors’ affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. RESULTS: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus’ origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. CONCLUSIONS: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short- and long-term.

negative: Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19) Importance: Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant: This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure: Cardiac involvement with COVID-19. Main Outcomes and Measures: Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results: An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance: This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

negative: Prognostic value of C-reactive protein in patients with COVID-19 Background Elevated serum C-reactive protein (CRP) level was observed in most patients with COVID-19. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from Jan 30 to Feb 20, 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. Results Out of 298 patients enrolled, 84 died and 214 recovered. Most non-survivors tended to be males, old aged, or with chronic diseases. Compared to survivors, non-survivors showed significantly higher white blood cell and neutrophil count, neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII, defined by platelet count multiply by NLR), CRP, procalcitonin, and D-dimer, and lower red blood cell, lymphocyte, and platelet count. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all p<0.05). With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%. Subgroup analysis revealed that CRP remained robust accuracy in adverse outcome prediction in patients with different disease severity (AUC 0.832, z=10.23, p<0.001; AUC 0.989, z=44.04, p<0.001). CRP was also an independent discriminator of severe/critical illness on admission (AUC 0.783, z=10.69, p<0.001). Conclusions In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.

negative: Improved survival outcome in SARs-CoV-2 (COVID-19) Acute Respiratory Distress Syndrome patients with Tocilizumab administration ABSTRACT Background: The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARs-CoV-2), was declared a global pandemic by the World Health Organization on March 11, 2020. Hence, there is an urgency to find effective treatment. Of those patients afflicted in the United States, many have required treatment with ventilator secondary to acute respiratory distress syndrome (ARDS). Data are needed regarding the benefit of treatment and prevention of the cytokine storms in COVID-19 patients with Tocilizumab. Methods: Clinical outcomes data for patients admitted to Orange Regional Medical Center with confirmed COVID-19 from Mar 15, 2020 to Apr 20, 2020 were identified through electronic health record chart review. We conducted a retrospective case-control study in confirmed COVID 19 positive patients with ARDS requiring mechanical ventilation and compared outcome in terms of mortality and length of stay amongst those who received Tocilizumab as treatment modality opposed to those that did not. Results: A total of 94 patients with COVID-19 ARDS were analyzed. 44 were in the study group and 50 in the control group. We tried to match both group as close as possible in terms of age, sex, BMI and HS score- calculated using inflammatory markers- ferritin, triglycerides, AST and fibrinogen. The median age was 55.5 years in the study group and 66 in the control group, difference was not statistically significant. Average HS score was 114 in the Tocilizumab group and 92 in the control group, difference was statistically significant with P<0.0001. Also, the patients in the study group had elevated levels of IL-6, triglycerides, AST, ferritin which were statistically significant with p < 0.0001 when compared to the control group. Length of stay was longer, average 17.9 days in the Tocilizumab. Survival rate was much lower at 48 % in the control group and 61.36 % in patients who received Tocilizumab with significant P value of < 0.00001. The number needed to treat (NNT) was 7.48, if we treat 8 patients with Tocilizumab, 1 will not die. Conclusions: Cytokine Release Syndrome (CRS) occurs in a large number of patients with severe COVID-19, which is also an important cause of death. IL- 6 is the key molecule of CRS, so IL-6R antagonist Tocilizumab may be of value in improving outcomes. In our study Tocilizumab group seemed to have improved survival outcome. Results have to be interpreted with caution since this is a retrospective study and mortality is affected by multiple, confounding factors. We await the results of ongoing randomized controlled trials to definitely answer the question of whether Tocilizumab improves survival in COVID-19 ARDS patients.

negative: Epidemic analysis of COVID-19 in China by dynamical modeling The outbreak of the novel coronavirus (2019-nCoV) epidemic has attracted world- wide attention. Herein, we propose a mathematical model to analyzes this epidemic, based on a dynamic mechanism that incorporating the intrinsic impact of hidden la- tent and infectious cases on the entire process of transmission. Meanwhile, this model is validated by data correlation analysis, predicting the recent public data, and back- tracking, as well as sensitivity analysis. The dynamical model reveals the impact of various measures on the key parameters of the epidemic. According to the public data of NHCs from 01/20 to 02/09, we predict the epidemic peak and possible end time for 5 different regions. The epidemic in Beijing and Shanghai, Mainland/Hubei and Hubei/Wuhan, are expected to end before the end of February, and before mid- March respectively. The model indicates that, the outbreak in Wuhan is predicted to be ended in the early April. As a result, more effective policies and more efforts on clinical research are demanded. Moreover, through the backtracking simulation, we infer that the outbreak of the epidemic in Mainland/Hubei, Hubei/Wuhan, and Wuhan can be dated back to the end of December 2019 or the beginning of January 2020.

negative: Alcohol use in times of the COVID 19: Implications for monitoring and policy Based on a literature search undertaken to determine the impacts of past public health crises, and a systematic review of the effects of past economic crises on alcohol consumption, two main scenarios—with opposite predictions regarding the impact of the current COVID‐19 pandemic on the level and patterns of alcohol consumption—are introduced. The first scenario predicts an increase in consumption for some populations, particularly men, due to distress experienced as a result of the pandemic. A second scenario predicts the opposite outcome, a lowered level of consumption, based on the decreased physical and financial availability of alcohol. With the current restrictions on alcohol availability, it is postulated that, for the immediate future, the predominant scenario will likely be the second, while the distress experienced in the first may become more relevant in the medium‐ and longer‐term future. Monitoring consumption levels both during and after the COVID‐19 pandemic will be necessary to better understand the effects of COVID‐19 on different groups, as well as to distinguish them from those arising from existing alcohol control policies.

negative: Chapter 15 Health Technology, Quality, Law, and Ethics Abstract Technology assessment capability is vital in determining health policy and priorities because science and technology changes occur rapidly and are essential for progress. Quality is promoted by high professional education and practice standards, accreditation by state and non governmental authorities for health provider institutions, public health departments as well as educational program for public health, health policy and health management. Quality is an ongoing challenge in health care and public health. New innovations and therapies change the nature of care and prevention, with important epidemic and epidemiologic effects. Adoption of new evidence based methods of prevention, diagnosis and therapy have and will continue to improve quality of life and longevity. Translation of scientific and technological advances into applied practice requires education of public health policy makers, and practitioners to be well trained to evaluate new evidence and keep up with rapidly changing capacity to address old and new challenges in public health. The context of public health is set in legal frameworks and ethical standards developed over many millennia, centuries and decades which need continuous revision in keeping with societal changes and norms. Law and ethics in public health reflect the societal values in the context of social, economic, demographic, epidemiologic and political changes, while facing new health challenges and new technologies. Health ethics needed to be reexamined in the light of medical participation in 20th century genocides in the name of racial purity and industrialized murder of millions in World War II. The Nuremberg Trials redefined ethics of health research and bioethics. Public health works to protect the population from illness and premature death, often with restrictions such as in cigarette advertisement and smoking. Failure to act in protection of public health can be unethical by denying best practices in health protection and health promotion.

negative: ¿Va a cambiar la neurología tras la pandemia de Covid-19 en los próximos cinco años?. Estudio de enfoque mediante informadores clave ]Abstract Introduction: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. Material and methods: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. Results: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. Conclusion: The key informant survey identified the foreseeable changes in neurological care after the pandemic.

negative: Energy performance of independent air dehumidification systems with energy recovery measures Independent air dehumidification provides an attractive alternative to traditional coupled air dehumidification with reduced energy use, better humidity control and indoor air quality. According to this concept, latent load is treated by an independent system and the sensible load is treated by chilled-ceiling panels. In this work, four independent air dehumidification systems with energy recovery strategies are proposed. They are as follows: system 1, mechanical dehumidification with heat pump; system 2, mechanical dehumidification with sensible heat exchanger; system 3, mechanical dehumidification with membrane-based total heat exchanger; and system 4: a heat pump incorporating an active desiccant wheel and evaporative cooler. They are compared with a mechanical dehumidification system with no heat recovery. Hour-by-hour energy analysis is performed on the systems proposed. The results show that the system of mechanical dehumidification with membrane total heat recovery (system 3) consumes the least primary energy. However, since, the systems employ energy recovery measures, the energy savings for the four systems are in the same order, around 4.40×10(6) kJ per person.

negative: Strategies for Pharmacological Organoprotection during Extracorporeal Circulation Targeting Ischemia-Reperfusion Injury Surgical correction of congenital cardiac malformations or aortocoronary bypass surgery in many cases implies the use of cardiopulmonary-bypass (CPB). However, a possible negative impact of CPB on internal organs such as brain, kidney, lung and liver cannot be neglected. In general, CPB initiates a systemic inflammatory response (SIRS) which is presumably caused by contact of blood components with the surface of CPB tubing. Moreover, during CPB the heart typically undergoes a period of cold ischemia, and the other peripheral organs a global low flow hypoperfusion. As a result, a plethora of pro-inflammatory mediators and cytokines is released activating different biochemical pathways, which finally may result in the occurrence of microthrombosis, microemboli, in depletion of coagulation factors and haemorrhagic diathesis besides typical ischemia-reperfusion injuries. In our review we will focus on possible pharmacological interventions in patients to decrease negative effects of CPB and to improve post-operative outcome with regard to heart and other organs like brain, kidney, or lung.

negative: COVID-19 virus outbreak forecasting of registered and recovered cases after sixty day lockdown in Italy: A data driven model approach Abstract Background Till 31 March 2020, 105,792 COVID-19 cases were confirmed in Italy including 15,726 deaths which explains how worst the epidemic has affected the country. After the announcement of lockdown in Italy on 9 March 2020, situation was becoming stable since last days of March. In view of this, it is important to forecast the COVID-19 evaluation of Italy condition and the possible effects, if this lock down could continue for another 60 days. Methods COVID-19 infected patient data has extracted from the Italian Health Ministry website includes registered and recovered cases from mid February to end March. Adoption of seasonal ARIMA forecasting package with R statistical model was done. Results Predictions were done with 93.75% of accuracy for registered case models and 84.4% of accuracy for recovered case models. The forecasting of infected patients could be reach the value of 182,757, and recovered cases could be registered value of 81,635 at end of May. Conclusions This study highlights the importance of country lockdown and self isolation in control the disease transmissibility among Italian population through data driven model analysis. Our findings suggest that nearly 35% decrement of registered cases and 66% growth of recovered cases will be possible.

negative: Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series Introduction: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Results: Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.

negative: Cardiovascular complications in COVID-19 Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

negative: Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection. OBJECTIVE To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.

negative: The Shifting Landscape of Genitourinary Oncology During the COVID-19 Pandemic and how Italian Oncologists Reacted: Results from a National Survey

negative: Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection Patients who survive influenza A (H7N9) virus infection are at risk of physical and psychological complications of lung injury and multi-organ dysfunction. However, there were no prospectively individualized assessments of physiological, functional and quality-of-life measures after hospital discharge. The current study aims to assess the main determinants of functional disability of these patients during the follow-up. Fifty-six influenza A (H7N9) survivors were investigated during the 2-year after discharge from the hospital. Results show interstitial change and fibrosis on pulmonary imaging remained 6 months after hospital discharge. Both ventilation and diffusion dysfunction improved, but restrictive and obstructive patterns on ventilation function test persisted throughout the follow-up period. For patients with acute respiratory distress syndrome lung functions improved faster during the first six months. Role-physical and Role-emotional domains in the 36-Item Short-Form Health Survey were worse than those of a sex- and age-matched general population group. The quality of life of survivors with ARDS was lower than those with no ARDS. Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital.

negative: Clinical and radiological outcome after mechanical thrombectomy in acute ischemic stroke: What matters? OBJECTIVE Recent studies have shown the efficacy of mechanical thrombectomy in acute ischemic stroke. We sought to identify prognostic parameters for clinical and radiological outcome after mechanical thrombectomy. METHODS In 34 patients (age 72 ± 13 years, 64.7% women) with acute occlusion of the distal ICA and/or M1 segment who were treated with mechanical thrombectomy, the Spearman correlation was performed to assess potential prognostic outcome parameters (age, NIHSS, ASPECT, thrombus length (TL), clot burden score (CBS), relative filling time delay (rFTD), time to recanalization (TTR) and TICI score). The modified Rankin scale (mRS) and the Alberta Stroke Program Early CT (ASPECT) score were used for clinical and radiological outcome, respectively. Receiver operating characteristic (ROC) analysis was performed to assess parameters predicting favorable clinical (ΔmRS ≤ 2) and radiological outcome (ΔASPECT ≤ 2). RESULTS Variables associated with favorable clinical outcome included NIHSS, TL, TTR and TICI score (p ≤ 0.01) with NIHSS ≤ 15 (p = 0.001, area under the curve (AUC) 0.87), TL ≤ 2 cm (p = 0.017, AUC 0.75), TTR ≤ 231 min (p = 0.001 AUC 0.88) and TICI ≥ 2b (p = 0.050, AUC 0.70). Shorter TTR and higher TICI scores were associated with favorable radiological outcome (p < 0.001) with TTR ≤ 224 min (p = 0.023, AUC 0.77) and TICI ≥ 2b (p = 0.000, AUC 0.86). CONCLUSION Fast and complete recanalization is essential to achieve a favorable radiological and functional outcome after mechanical thrombectomy in acute ischemic stroke. Age, CBS and collateral supply play a subordinate role.

negative: Cardiovascular Pharmacology in the Time of COVID-19: A Focus on Angiotensin-Converting Enzyme 2 Coronavirus disease-2019 (COVID-19) has emerged as a pandemic affecting millions of adults. Severe acute respiratory syndrome coronavirus-2019 (SARS-CoV-2), the causative virus of COVID-19, infects host cells through angiotensin-converting enzyme 2 (ACE2). Preclinical models suggest that ACE2 upregulation confers protective effects in acute lung injury. In addition, renin–angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease outcomes, but may increase ACE2 levels. We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology, as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin–angiotensin–aldosterone system inhibitor therapy.

negative: Heralding Healthcare Professionals: Recognition of Neurological Deficits in COVID-19 The 2019 novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic disease that is dominated by pulmonary symptoms. However, recent reports of isolation of the virus from cerebrospinal fluid (CSF) coupled with radiological evidence of zones of necrosis in the brain, have elucidated the neurotropic potential of SARS-CoV-2. The acute respiratory failure seen in patients with COVID-19 is alarming and could be due to the effects of SARS-CoV-2 on the central respiratory regulatory centers in the brainstem. Appropriate interventions can be implemented to prevent severe outcomes of neurological invasion by SARS-CoV-2 to reduce the morbidity and mortality of patients with COVID-19. It is of paramount importance that the scientific community alerts the healthcare professionals of the pieces of evidence that can herald them on the covert neurological deficits in progress in COVID-19.

negative: Analysing recovery from pandemics by Learning Theory: the case of CoVid-19 We present a method for predicting the recovery time from infectious diseases outbreaks such as the recent CoVid-19 virus. The approach is based on the theory of learning from errors, specifically adapted to the control of the virus spread by reducing infection rates using countermeasures such as medical treatment, isolation, social distancing etc. When these are effective, the infection rate, after reaching a peak, declines following a given recovery rate curve. We use presently available data from China, South Korea and others to make actual predictions of the time needed for securing minimum infection rates in the future.

negative: B5/133 – Longer-term follow up of aerobic capacity in children affected by Severe Acute Respiratory Syndrome (SARS)

negative: COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients.

negative: Emergence of Novel Coronavirus and COVID-19: whether to stay or die out? The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus “SARS-CoV-2” (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

negative: Determinants of cardiac adverse events of chloroquine and hydroxychloroquine in 20 years of drug safety surveillance reports Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to the risk of drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.

negative: Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020 Since December 2019, 62 medical staff of Zhongnan Hospital in Wuhan, China have been hospitalised with coronavirus disease 2019. During the post-discharge surveillance after clinical recovery, swabs were positive in two asymptomatic cases (3.23%). Case 1 had presented typical clinical and radiological manifestations on admission, while manifestation in Case 2 was very mild. In conclusion, a small proportion of recovered patients may test positive after discharge, and post-discharge surveillance and isolation need to be strengthened.

negative: Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study BACKGROUND: The medical, societal, and economic impact of the coronavirus disease 2019 (COVID-19) pandemic has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom thus far have underlying conditions. Models have not incorporated information on high-risk conditions or their longer-term baseline (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on varying levels of transmission suppression and differing mortality impacts based on different relative risks for the disease. METHODS: In this population-based cohort study, we used linked primary and secondary care electronic health records from England (Health Data Research UK–CALIBER). We report prevalence of underlying conditions defined by Public Health England guidelines (from March 16, 2020) in individuals aged 30 years or older registered with a practice between 1997 and 2017, using validated, openly available phenotypes for each condition. We estimated 1-year mortality in each condition, developing simple models (and a tool for calculation) of excess COVID-19-related deaths, assuming relative impact (as relative risks [RRs]) of the COVID-19 pandemic (compared with background mortality) of 1·5, 2·0, and 3·0 at differing infection rate scenarios, including full suppression (0·001%), partial suppression (1%), mitigation (10%), and do nothing (80%). We also developed an online, public, prototype risk calculator for excess death estimation. FINDINGS: We included 3 862 012 individuals (1 957 935 [50·7%] women and 1 904 077 [49·3%] men). We estimated that more than 20% of the study population are in the high-risk category, of whom 13·7% were older than 70 years and 6·3% were aged 70 years or younger with at least one underlying condition. 1-year mortality in the high-risk population was estimated to be 4·46% (95% CI 4·41–4·51). Age and underlying conditions combined to influence background risk, varying markedly across conditions. In a full suppression scenario in the UK population, we estimated that there would be two excess deaths (vs baseline deaths) with an RR of 1·5, four with an RR of 2·0, and seven with an RR of 3·0. In a mitigation scenario, we estimated 18 374 excess deaths with an RR of 1·5, 36 749 with an RR of 2·0, and 73 498 with an RR of 3·0. In a do nothing scenario, we estimated 146 996 excess deaths with an RR of 1·5, 293 991 with an RR of 2·0, and 587 982 with an RR of 3·0. INTERPRETATION: We provide policy makers, researchers, and the public a simple model and an online tool for understanding excess mortality over 1 year from the COVID-19 pandemic, based on age, sex, and underlying condition-specific estimates. These results signal the need for sustained stringent suppression measures as well as sustained efforts to target those at highest risk because of underlying conditions with a range of preventive interventions. Countries should assess the overall (direct and indirect) effects of the pandemic on excess mortality. FUNDING: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Health Data Research UK.

negative: Mental health during the coronavirus disease 2019 (Covid-19) pandemic: more is still to be done

negative: Association of inflammatory markers with the severity of COVID-19 Background: The ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction. Aims: In the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods: The following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = -8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.

negative: Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

negative: COVID-19 and telepsychiatry: an evidence-based guidance for clinicians. BACKGROUND COVID-19 presents unique challenges in healthcare, including mental health care provision. Telepsychiatry can provide an alternative to face to face assessment and can also be used creatively with other technologies to enhance care, but clinicians and patients may feel underconfident about embracing this new way of working. OBJECTIVE The aim was to produce an open access, easy-to-consult and reliable source of information and guidance about telepsychiatry and COVID-19 using an evidence-based approach. METHODS We systematically searched existing English language guidelines and websites for information on telepsychiatry in the context of COVID-19 up to and including May 2020. We used broad search criteria and included pre-COVID-19 guidelines and also other digital mental health topics where relevant. We summarised the data we extracted as answers to specific clinical questions. RESULTS Findings from this study are presented as both a short practical checklist for clinicians and a detailed table with a full summary of all the guidelines. The summary tables are also available on an open access webpage (https://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/table-5-digital-technologies-and-telepsychiatry/) which is regularly updated. These findings reflect the strong evidence base for the use of telepsychiatry and include guidelines for many of the common concerns expressed by clinicians about practical implementation, technology, information governance and safety. Guidelines across countries differ significantly, with UK guidelines more conservative and focussed on practical implementation, and US guidelines more expansive and detailed. Guidelines on possible combination with other digital technologies such as apps, for example from the FDA, NHS Apps Library and NICE are less detailed. Several key areas were not represented. Whilst some special populations such as child and adolescent, older adult and cultural issues are specifically included, important populations such as learning disabilities, psychosis, personality disorder and eating disorders, which may present particular challenges for telepsychiatry, are not. In addition, initial consultation and follow-up sessions are not clearly distinguished. Finally, a hybrid model of care (combining telepsychiatry with other technologies and in-person care) is not explicitly covered by the existing guidelines. CONCLUSIONS We produced a comprehensive synthesis of guidance answering a wide range of clinical questions in telepsychiatry. This meets the urgent need for practical information for both clinicians and health care organisations who are rapidly adapting to the pandemic and implementing remote consultation. It reflects variations across countries and can be used as a basis for organisational change in the short and longer term. Providing easily accessible guidance is a first step, but will need cultural change to implement, as clinicians start to view telepsychiatry not just as a replacement, but as a parallel and complimentary form of delivering therapy, with its own advantages and benefits as well as restrictions. A combination or hybrid approach can be the most successful approach in the new world of mental health post-COVID-19 and guidance will need to expand to encompass the use of telepsychiatry in conjunction with other in-person and digital technologies, and also its use across all psychiatric disorders, not just those who are the first to access and engage with remote treatment. CLINICALTRIAL

negative: Influenza-associated pneumonia as reference to assess seriousness of coronavirus disease (COVID-19) Information on severity of coronavirus disease (COVID-19) (transmissibility, disease seriousness, impact) is crucial for preparation of healthcare sectors. We present a simple approach to assess disease seriousness, creating a reference cohort of pneumonia patients from sentinel hospitals. First comparisons exposed a higher rate of COVID-19 patients requiring ventilation. There were more case fatalities among COVID-19 patients without comorbidities than in the reference cohort. Hospitals should prepare for high utilisation of ventilation and intensive care resources.

negative: Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO(2) of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups - age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.

negative: Health Information–Seeking Patterns of the General Public and Indications for Disease Surveillance: Register-Based Study Using Lyme Disease BACKGROUND: People using the Internet to find information on health issues, such as specific diseases, usually start their search from a general search engine, for example, Google. Internet searches such as these may yield results and data of questionable quality and reliability. Health Library is a free-of-charge medical portal on the Internet providing medical information for the general public. Physician’s Databases, an Internet evidence-based medicine source, provides medical information for health care professionals (HCPs) to support their clinical practice. Both databases are available throughout Finland, but the latter is used only by health professionals and pharmacies. Little is known about how the general public seeks medical information from medical sources on the Internet, how this behavior differs from HCPs’ queries, and what causes possible differences in behavior. OBJECTIVE: The aim of our study was to evaluate how the general public’s and HCPs’ information-seeking trends from Internet medical databases differ seasonally and temporally. In addition, we aimed to evaluate whether the general public’s information-seeking trends could be utilized for disease surveillance and whether media coverage could affect these seeking trends. METHODS: Lyme disease, serving as a well-defined disease model with distinct seasonal variation, was chosen as a case study. Two Internet medical databases, Health Library and Physician’s Databases, were used. We compared the general public’s article openings on Lyme disease from Health Library to HCPs’ article openings on Lyme disease from Physician’s Databases seasonally across Finland from 2011 to 2015. Additionally, media publications related to Lyme disease were searched from the largest and most popular media websites in Finland. RESULTS: Both databases, Health Library and Physician’s Databases, show visually similar patterns in temporal variations of article openings on Lyme disease in Finland from 2011 to 2015. However, Health Library openings show not only an increasing trend over time but also greater fluctuations, especially during peak opening seasons. Outside these seasons, publications in the media coincide with Health Library article openings only occasionally. CONCLUSIONS: Lyme disease–related information-seeking behaviors between the general public and HCPs from Internet medical portals share similar temporal variations, which is consistent with the trend seen in epidemiological data. Therefore, the general public’s article openings could be used as a supplementary source of information for disease surveillance. The fluctuations in article openings appeared stronger among the general public, thus, suggesting that different factors such as media coverage, affect the information-seeking behaviors of the public versus professionals. However, media coverage may also have an influence on HCPs. Not every publication was associated with an increase in openings, but the higher the media coverage by some publications, the higher the general public’s access to Health Library.

negative: Dynamic changes of serum SARS-Coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. METHODS: The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT) examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [D(L)CO] < 80% of predicted value [pred]) received regular lung function tests and HRCT examinations in the follow-up phase in order to document the changes in their lung condition. Some patients who complained of joint pain were given magnetic resonance imaging (MRI) examinations of their femoral heads. FINDINGS: Of all the subjects, 81.2% (311 of 383 patients) tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients) were suffering from lung diffusion abnormities (D(L)CO < 80% pred) and 21.5% (67 of 311 patients) exhibited lung fibrotic changes. In the 12 month duration of this study, all of the 40 patients with lung diffusion abnormities who were examined exhibited some improvement of lung function and fibrosis detected by radiography. Of the individuals receiving MRI examinations, 23.1% (18 of 78 patients) showed signs of femoral head necrosis. INTERPRETATION: The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.

negative: Nottingham Trent University and Makerere University School of Public Health partnership: experiences of co-learning and supporting the healthcare system in Uganda Partnerships between developed and developing country institutions are increasingly becoming important in addressing contemporary global health challenges faced by health systems. Inter-university health collaboration such as the Nottingham Trent University (UK) and Makerere University School of Public Health (Uganda) partnership provide opportunities for working together in training, research and service delivery while strengthening health systems. This paper shares the experiences, achievements and opportunities of this partnership in co-learning and supporting the health system in Uganda. This includes a project being implemented to strengthen the training, supervision and motivation of community health workers in rural Uganda. Training and research are a key focus of the partnership and have involved both staff and students of both institutions including guest lectures, seminars and conference presentations. The partnership’s collaboration with stakeholders such as the Ministry of Health (Uganda) and local health authorities has ensured participation necessary in supporting implementation of sustainable interventions. The partnership uses several channels such as email, telephone, Skype, Dropbox and WhatsApp which have been useful in maintaining constant and effective communication. The challenges faced by the partnership include lack of funding to support student mobility, and varying academic schedules of the two institutions. The experiences and prospects of this growing partnership can inform other collaborations in similar settings.

negative: Estimation of the probability of reinfection with COVID-19 coronavirus by the SEIRUS model With sensitivity of the Polymerase Chain Reaction (PCR) test used to detect the presence of the virus in the human host, the global health community has been able to record a great number of recovered population. Therefore, in a bid to answer a burning question of reinfection in the recovered class, the model equations which exhibits the disease-free equilibrium (E_0 ) state for COVID-19 coronavirus was developed in this study and was discovered to both exist as well as satisfy the criteria for a locally or globally asymptotic stability with a basic reproductive number R_0=0 for and endemic situation. Hence, there is a chance of no secondary reinfections from the recovered population as the rate of incidence of the recovered population vanishes, that is, B=0. Furthermore, numerical simulations were carried to complement the analytical results in investigating the effect of the implementation of quarantine and observatory procedures has on the projection of the further spread of the virus globally. Result shows that the proportion of infected population in the absence of curative vaccination will continue to grow globally meanwhile the recovery rate will continue slowly which therefore means that the ratio of infection to recovery rate will determine the death rate that is recorded globally and most significant for this study is the rate of reinfection by the recovered population which will decline to zero over time as the virus is cleared clinically from the system of the recovered class.

negative: COVID-19: a new virus, but an old cytokine release syndrome Understanding the cell entry mechanism of pandemic coronavirus SARS-CoV-2 is crucial for treating the disease Zhou et al (Nature) and Hoffmann et al (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2 These results suggest several possible therapeutic targets, including the IL-6-STAT3 axis previously associated with cytokine release syndromes

negative: Confronting Another Pandemic: Lessons from HIV can Inform Our COVID-19 Response The novel coronavirus 2019 illness (COVID-19) has completely transformed and uprooted lives across the globe. While different diseases, there are critical observations and lessons to be learned from the ongoing HIV epidemic to inform our response to COVID-19. We reflect on how this relates to (1) testing, including contact tracing; (2) health system redesign; (3) telehealth; (4) health disparities; (5) political denial, with inadequate and uncoordinated governmental response; (6) occupational exposure; and (7) complex reactions among healthcare providers. Decades of experiences with HIV provide an important framework for moving forward as we combat COVID-19.

negative: A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of Î±-Lipoic acid for critically ill patients with coronavirus disease 2019(COVID-19) Object: To evaluate the clinical efficacy and safety of -Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19). Methods: A randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days. Result: Nine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P=0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P=0.09). Conclusion: In our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19. Keywords: Pneumonia; COVID-19; SARS-CoV-2 ; -Lipoic acid

negative: Travel health risk perceptions of Chinese international students in Australia – Implications for COVID-19 Abstract Background International students frequently return to their country of origin to visit friends and relatives (VFR), and are at increased risk of travel-associated infections. Little is known of their travel health seeking behaviours. China is the biggest source of international students studying in Australia and the unprecedented epidemic of COVID-19 in China makes this an important area of research. Methods Focus groups of Chinese international students were conducted to explore travel health-related knowledge, attitudes and practices. Eligible participants were studying in Sydney, and had travelled to China and Hong Kong to visit friends and relatives in the preceding 18 months. A variety of topics were explored, using a focus group guide. Thematic analysis was undertaken on the transcripts using nVivo software. The list of codes and themes were not pre-determined but developed through content analysis. Results Two focus groups were held with a total of 28 participants. Risk perception about VFR travel was generally low among Chinese international students. Pre-travel healthcare was not sought. Students strongly relied on the Internet, social media, parents and friends in China for travel health advice. Conclusion This research provides insights into Chinese international students as VFR travellers. It confirms students could be a risk population for importations of infections such as COVID-19 because of low risk perception and lack of seeking travel health advice. This can inform health promotion strategies for students.

negative: Identification of critical airports for controlling global infectious disease outbreaks: Stress-tests focusing in Europe Abstract As the global population increases and transportation connectivity improves in quality and prices, the demand for mobility increases, especially in long-haul services. According to the 2017 report of the European Commission in Mobility and Transport, the performance of all modes for passenger transport (roadways and airways) are reaching record highs. Although the benefits of the increased demand for mobility are substantial and welcome, an effort should be paid such as to ameliorate possible threatening side-effects that may also arise. As World Health Organization (WHO) denotes and as has been evident from the global COVID-19 epidemic outbreak, infectious diseases can be spread directly or indirectly from one person to another under common exposure circumstances such as air transportation (especially long-haul airline connections) that may act as the medium for transmitting and spreading infectious diseases. In this paper, analytical and realistic models have been integrated, for providing evidence on the spread dynamics of infectious diseases that may face Europe through the airlines system. In particular, a detailed epidemiological model has been integrated with the airlines’ and land transport network, able to simulate the epidemic spread of infectious diseases originated from distant locations. Additionally, a wide set of experiments and simulations have been conducted, providing results from detailed stress-tests covering both mild as well as aggressive cases of epidemic spreading scenarios. The results provide convincing evidence on the effectiveness that the European airports' system offer in controlling the emergence of epidemics, but also on the time and extent that controlling measures should be taken in order to break the chain of infections in realistic cases.

negative: Prediction of the COVID-19 Pandemic for the Top 15 Affected Countries: Advanced Autoregressive Integrated Moving Average (ARIMA) Model BACKGROUND: The coronavirus disease (COVID-19) pandemic has affected more than 200 countries and has infected more than 2,800,000 people as of April 24, 2020. It was first identified in Wuhan City in China in December 2019. OBJECTIVE: The aim of this study is to identify the top 15 countries with spatial mapping of the confirmed cases. A comparison was done between the identified top 15 countries for confirmed cases, deaths, and recoveries, and an advanced autoregressive integrated moving average (ARIMA) model was used for predicting the COVID-19 disease spread trajectories for the next 2 months. METHODS: The comparison of recent cumulative and predicted cases was done for the top 15 countries with confirmed cases, deaths, and recoveries from COVID-19. The spatial map is useful to identify the intensity of COVID-19 infections in the top 15 countries and the continents. The recent reported data for confirmed cases, deaths, and recoveries for the last 3 months was represented and compared between the top 15 infected countries. The advanced ARIMA model was used for predicting future data based on time series data. The ARIMA model provides a weight to past values and error values to correct the model prediction, so it is better than other basic regression and exponential methods. The comparison of recent cumulative and predicted cases was done for the top 15 countries with confirmed cases, deaths, and recoveries from COVID-19. RESULTS: The top 15 countries with a high number of confirmed cases were stratified to include the data in a mathematical model. The identified top 15 countries with cumulative cases, deaths, and recoveries from COVID-19 were compared. The United States, the United Kingdom, Turkey, China, and Russia saw a relatively fast spread of the disease. There was a fast recovery ratio in China, Switzerland, Germany, Iran, and Brazil, and a slow recovery ratio in the United States, the United Kingdom, the Netherlands, Russia, and Italy. There was a high death rate ratio in Italy and the United Kingdom and a lower death rate ratio in Russia, Turkey, China, and the United States. The ARIMA model was used to predict estimated confirmed cases, deaths, and recoveries for the top 15 countries from April 24 to July 7, 2020. Its value is represented with 95%, 80%, and 70% confidence interval values. The validation of the ARIMA model was done using the Akaike information criterion value; its values were about 20, 14, and 16 for cumulative confirmed cases, deaths, and recoveries of COVID-19, respectively, which represents acceptable results. CONCLUSIONS: The observed predicted values showed that the confirmed cases, deaths, and recoveries will double in all the observed countries except China, Switzerland, and Germany. It was also observed that the death and recovery rates were rose faster when compared to confirmed cases over the next 2 months. The associated mortality rate will be much higher in the United States, Spain, and Italy followed by France, Germany, and the United Kingdom. The forecast analysis of the COVID-19 dynamics showed a different angle for the whole world, and it looks scarier than imagined, but recovery numbers start looking promising by July 7, 2020.

negative: Information Mining for COVID-19 Research From a Large Volume of Scientific Literature The year 2020 has seen an unprecedented COVID-19 pandemic due to the outbreak of a novel strain of coronavirus in 180 countries. In a desperate effort to discover new drugs and vaccines for COVID-19, many scientists are working around the clock. Their valuable time and effort may benefit from computer-based mining of a large volume of health science literature that is a treasure trove of information. In this paper, we have developed a graph-based model using abstracts of 10,683 scientific articles to find key information on three topics: transmission, drug types, and genome research related to coronavirus. A subgraph is built for each of the three topics to extract more topic-focused information. Within each subgraph, we use a betweenness centrality measurement to rank order the importance of keywords related to drugs, diseases, pathogens, hosts of pathogens, and biomolecules. The results reveal intriguing information about antiviral drugs (Chloroquine, Amantadine, Dexamethasone), pathogen-hosts (pigs, bats, macaque, cynomolgus), viral pathogens (zika, dengue, malaria, and several viruses in the coronaviridae virus family), and proteins and therapeutic mechanisms (oligonucleotide, interferon, glycoprotein) in connection with the core topic of coronavirus. The categorical summary of these keywords and topics may be a useful reference to expedite and recommend new and alternative directions for COVID-19 research.

negative: Dioctophyma renale in a dog: Clinical diagnosis and surgical treatment Abstract This study reports a case of parasitism by the giant kidney worm, Dioctophyma renale, diagnosed in the right kidney of a domestic dog. An adult female German Shepherd was attended with clinical history of prostration and hyporexia. The hemogram showed changes compatible with an inflammatory process, for that reason, an abdominal ultrasound was requested. Ultrasound image suggested the presence of D. renale in the right kidney. The diagnosis was confirmed after urinalysis due to the presence of dioctophymas ova in the urinary sediment. Surgical treatment was made and the animal had an excellent recovery after the nephrectomy was performed. Generally, in almost all cases, parasitism by D. renale in domestic dogs is a necropsy finding, nevertheless imaging techniques as sonography and laboratorial exams as urinalysis have been proven to be important tools to achieve diagnosis. The purpose of this study is to report a case of parasitism by D. renale where diagnosis and treatment were made in time to allow the patient's recovery.

negative: Neurovascular Complications in COVID-19 Infection: Case Series We present a series of 10 hospitalized patients with confirmed coronavirus 2019 infections who developed severe neurovascular complications and discuss the possible reasons for these findings and their relationship to the novel Severe Acute Respiratory Syndrome coronavirus 2 infection.

negative: Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: a retrospective cohort study Background: COVID-19 is still becoming an increasing global threat to public health. More detailed and specific characteristics of COVID-19 are needed to better understand this disease. Additionally, durations of COVID-19, e.g., the average time from exposure to recovery, which is of great value in understanding this disease, has not been reported so far. Aims: To give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration. Methods: In this retrospective study, we enrolled 77 patients (mean age: 52 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical and radiological data on admission were collected; complications and outcomes were followed up until 29th February 2020. The study endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration. Results: Of 77 patients, there are 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home after being tested negative for SARS-CoV-2 infections, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed bilateral pneumonia on CT scan, shorter time from the illness onset to admission, the severity of disease and lymphopenia were independently associated with longer hospitalized duration. Conclusions: COVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, the severity of disease are the risk factors for longer hospitalization duration of COVID-19.

negative: Coronavirus research before 2020 is more relevant than ever, especially when interpreted for COVID-19 The speed with which biomedical researchers were able to identify and characterise COVID-19 was clearly due to prior research with other coronaviruses. Early epidemiological comparisons with two previous coronaviruses, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), also made it easier to predict COVID-19's likely spread and lethality. This article assesses whether academic interest in prior coronavirus research has translated into interest in the primary source material, using Mendeley reader counts for early academic impact evidence. The results confirm that SARS and MERS research 2008-2017 experienced anomalously high increases in Mendeley readers in April-May 2020. Nevertheless, studies learning COVID-19 lessons from SARS and MERS or using them as a benchmark for COVID-19 have generated much more academic interest than primary studies of SARS or MERS. Thus, research that interprets prior relevant research for new diseases when they are discovered seems to be particularly important to help researchers to understand its implications in the new context.

negative: Preserving stroke care during the COVID-19 pandemic: Potential issues and solutions The corona virus 2019 (COVID-19) pandemic requires drastic changes in allocation of resources which can affect the delivery of stroke care, and many providers are seeking guidance. As caregivers, we are guided by 3 distinct principles that will occasionally conflict during the pandemic: (1) We must ensure the best care for those stricken with COVID-19, (2) We must provide excellent care and advocacy for patients with cerebrovascular disease and their families, and (3) We must advocate for the safety of healthcare personnel managing patients with stroke, with particular attention to those most vulnerable, including trainees. This descriptive review by a diverse group of experts in stroke care aims to provide advice by specifically addressing the potential impact of this pandemic on: (1) the quality of the stroke care delivered, (2) ethical considerations in stroke care, (3) safety & logistic issues for providers of stroke patients, and (4) stroke research. Our recommendations on these issues represent our best opinions given the available information, but are subject to revision as the situation related to the COVID-19 pandemic continues to evolve. We expect that ongoing emergent research will offer additional insights that will provide evidence that could prompt the modification or removal of some of these recommendations.

negative: Nifedipine and Amlodipine Are Associated With Improved Mortality and Decreased Risk for Intubation and Mechanical Ventilation in Elderly Patients Hospitalized for COVID-19 Dihydropyridine calcium channel blockers (CCB) are typically used agents in the clinical management of hypertension. Yet, they have also been utilized in the treatment of various pulmonary disorders with vasoconstriction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in the development of vasoconstrictive, proinflammatory, and pro-oxidative effects. A retrospective review was conducted on CCB use in hospitalized patients in search of any difference in outcomes related to specific endpoints: survival to discharge and progression of disease leading to intubation and mechanical ventilation. The electronic medical records for all patients that tested positive for SARS-CoV-2 that were at or above the age of 65 and that expired or survived to discharge from a community hospital in Brooklyn, NY, between the start of the public health crisis due to the viral disease up until April 13, 2020, were included. Of the 77 patients that were identified, 18 survived until discharge and 59 expired. Seven patients from the expired group were excluded since they died within one day of presentation to the hospital. Five patients were excluded from the expired group since their age was above that of the eldest patient in the survival group (89 years old). With 65 patients left, 24 were found to have been administered either amlodipine or nifedipine (CCB group) and 41 were not (No-CCB group). Patients treated with a CCB were significantly more likely to survive than those not treated with a CCB: 12 (50%) survived and 12 expired in the CCB group vs. six (14.6%) that survived and 35 (85.4%) that expired in the No-CCB treatment group (P<.01; p=0.0036). CCB patients were also significantly less likely to undergo intubation and mechanical ventilation. Only one patient (4.2%) was intubated in the CCB group whereas 16 (39.0%) were intubated in the No-CCB treatment group (P<.01; p=0.0026). Nifedipine and amlodipine were found to be associated with significantly improved mortality and a decreased risk for intubation and mechanical ventilation in elderly patients hospitalized with COVID-19. Further clinical studies are warranted. Including either nifedipine or amlodipine in medication regimens for elderly patients with hypertension hospitalized for COVID-19 may be considered.

negative: Coronavirus disease 2019 (COVID-19) pneumonia in a hemodialysis patient: A case report RATIONALE: The 2019 novel coronavirus disease (COVID-19) causes a novel, atypical pneumonia that has brought huge public health challenges across the globe. There is limited data about patients with end-stage renal disease who also suffer from COVID-19. In this report, we discuss the case of a hemodialysis patient who developed COVID-19 pneumonia in the clinical course. PATIENT CONCERNS: A 79-year-old man who had end-stage renal disease (ESRD) and was taking regular hemodialysis was admitted to hospital for a fever and dry cough. The patient, who also had cardiovascular disease, had no history of contact with COVID-2019 patients. DIAGNOSIS: The patient was diagnosed with COVID-2019 by the reverse-transcriptase polymerase chain reaction (RT-PCR), and his pharyngeal swab for SARS-CoV-2 was positive. INTERVENTION: The treatment was mainly supportive and the patient was intensively monitored. He was treated with oxygen, broad-spectrum antibiotics, antiviral drugs, and methylprednisolone. The patient took continuous renal replacement therapy (CRRT) every 2 days. OUTCOMES: After 19 days, an RT-PCR assay for SARS-CoV-2 was negative, and computed tomography (CT) of the patient's thorax indicated that the pulmonary inflammatory exudation was absorbed and pulmonary infection improved significantly. He was discharged on day 29 after recovering from COVID-2019 pneumonia. LESSONS: The courses of disease and treatment options for this individual were significantly more complicated than those for ordinary patients. Therefore, it was necessary to monitor the condition of the patient closely and to protect the dialysis unit staff from being infected. Compared with other severe COVID-2019 cases, this patient recovered more quickly following treatment, which was likely due to the removal of inflammatory mediators by CRRT. This implies that blood purification might be an important option for hemodialysis patients with COVID-19.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: Clinical outcomes in COVID-19 patients treated with tocilizumab: An individual patient data systematic review BACKGROUND: Current evidence suggests an important role of the interleukin-6 (IL-6) pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cytokine release storm in severely ill coronavirus disease 2019 (COVID-19) patients. Inhibition of the IL-6 pathway with tocilizumab has been employed successfully in some of these patients but the data is mostly consistent of case reports and series. METHODS: We performed a systematic search of PubMed, Embase, and Medline from 22nd April 2020 and again on 27th April 2020 using the following search terms alone or in combination: "COVID-19," "coronavirus," "SARS-CoV-2," "COVID," "anti-interleukin-6 receptor antibodies," "anti-IL-6," "tocilizumab," "sarilumab," "siltuximab." We included studies that reported individual patient data. We extracted and analyzed individual level data on baseline characteristics, laboratory findings, and clinical outcomes. The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital complications, recovery rates, effect of patient characteristics on the primary outcome and changes in levels of inflammatory markers. RESULTS: Three hundred fifty-two records were identified through a systematic search, of which 10 studies met the inclusion criteria. A single study currently under review was also added. Eleven observational studies encompassing 29 patients were included in the present review. There were more males (24 [82.8%]), and hypertension was the most common comorbidity (16 [48.3%]). Over an average of 5.4 hospital days, the primary endpoint occurred in 6 (20.7%) patients. Among surviving patients, about 10% had worsened disease and 17% recovered. The most common complication was acute respiratory distress syndrome (8 [27.6%]). The IL-6 level was significantly higher after the initiation of tocilizumab with median (interquartile range) of 376.6 (148-900.6) pg/mL compared to the baseline of 71.1 (31.9-122.8) pg/mL (P = .002). Mean (standard deviation) levels of C-reactive protein (CRP) were significantly decreased following treatment 24.6 (26.9) mg/L compared to baseline 140.4 (77) mg/L (P < .0001). Baseline demographics were not significantly different among survivors and nonsurvivors by Fisher's exact test. CONCLUSION: In COVID-19 patients treated with tocilizumab, IL-6 levels are significantly elevated, which are supportive of cytokine storm. Following initiation of tocilizumab, there is elevation in the IL-6 levels and CRP levels dramatically decrease, suggesting an improvement in this hyperinflammatory state. Ongoing randomized control trials will allow for further evaluation of this promising therapy. IMPORTANCE: Recent data indicate that severe COVID-19 causes a cytokine release storm and is associated with worse clinical outcomes and IL-6 plays an important role. It is suggestive that anti-IL-6 results in the improvement of this hyperinflammatory state. However, to our knowledge, there is no individual patient data systematic review performed to summarize baseline characteristics and clinical outcomes of COVID-19 patients who received tocilizumab.

negative: Elevated troponin in patients with Coronavirus Disease 2019 (COVID-19): possible mechanisms Abstract Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems due to the high proportion of critical presentations, and resulted in over 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

negative: There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health

negative: COVID-19 Information Seeking on Digital Media and Preventive Behaviors: The Mediation Role of Worry. The high prevalence of novel coronavirus disease (COVID-19) and inefficient preventive measures taken to curb the disease are significant public health concerns. Rapid and innovative advances in digital media offer opportunities for health education, which could result in increased preventive behaviors. This study assessed preventive behaviors against contracting COVID-19 and tested mediation pathways linking four types of digital media consumption (social media, mobile social networking apps [MSNs], online news media, and social live steaming services [SLSSs]) to preventive behaviors, mediated by worry. Results from an online survey (N = 511) revealed that the vast majority (>90 percent) of respondents had very often or always practiced preventive behaviors against contracting COVID-19 such as washing their hands more regularly with soap and water, staying away from crowded places, and wearing face masks out in public. In addition, COVID-19 information seeking through the four types of digital media was a salient parameter that encouraged people to practice preventive behaviors either directly or indirectly. Specifically, seeking COVID-19-related information on MSNs, SLSSs, and online news media was directly associated with preventive behaviors. Whereas COVID-19 information consumption on social media, MSNs, and SLSSs during the infectious disease outbreak could elicit intense worry and, in turn, increase preventive behaviors. The reasons for and implications of the results are discussed.

negative: Protease inhibitors broadly effective against feline, ferret and mink coronaviruses Abstract Ferret and mink coronaviruses typically cause catarrhal diarrhea in ferrets and minks, respectively. In recent years, however, systemic fatal coronavirus infection has emerged in ferrets, which resembles feline infectious peritonitis (FIP) in cats. FIP is a highly fatal systemic disease caused by a virulent feline coronavirus infection in cats. Despite the importance of coronavirus infections in these animals, there are no effective commercial vaccines or antiviral drugs available for these infections. We have previously reported the efficacy of a protease inhibitor in cats with FIP, demonstrating that a virally encoded 3C-like protease (3CLpro) is a valid target for antiviral drug development for coronavirus infections. In this study, we extended our previous work on coronavirus inhibitors and investigated the structure-activity relationships of a focused library of protease inhibitors for ferret and mink 3CLpro. Using the fluorescence resonance energy transfer assay, we identified potent inhibitors broadly effective against feline, ferret and mink coronavirus 3CLpro. Multiple amino acid sequence analysis and modelling of 3CLpro of ferret and mink coronaviruses were conducted to probe the structural basis for these findings. The results of this study provide support for further research to develop broad-spectrum antiviral agents for multiple coronavirus infections. To the best of our knowledge, this is the first report on small molecule inhibitors of ferret and mink coronaviruses.

negative: Current Understanding of COVID-19 Clinical Course and Investigational Treatments Importance: Currently, there is no unified framework linking disease progression to established viral levels, clinical tests, inflammatory markers, and investigational treatment options. Objective: It may take many weeks or months to establish a standard treatment approach. Given the growing morbidity and mortality with respect to COVID-19, we present a treatment approach based on a thorough review of scholarly articles and clinical reports. Our focus is on staged progression, clinical algorithms, and individualized treatment. Evidence Review: We followed the protocol for a quality review article proposed by Heyn et. al.1 A literature search was conducted to find all relevant studies related to COVID-19. The search was conducted between April 1, 2020 and April 13, 2020 using the following electronic databases: PubMed (1809 to present), Google Scholar (1900 to present), MEDLINE (1946 to present), CINAHL (1937 to present), and Embase (1980 to present). Keywords used included COVID-19, 2019-nCov, SARS-CoV-2, SARS-CoV, and MERS-CoV, with terms such as efficacy, seroconversion, microbiology, pathophysiology, viral levels, inflammation, survivability, and treatment and pharmacology. No language restriction was placed on the search. Reference lists were manually scanned for additional studies. Findings: Of the articles found in the literature search, 70 were selected for inclusion in this study (67 cited in the body of the manuscript and 3 additional unique references in the Figures). The articles represent work from China, Japan, Taiwan, Vietnam, Rwanda, Israel, France, the United Kingdom, the Netherlands, Canada, and the United States. Most of the articles were cohort or case studies, but we also drew upon information found in guidelines from hospitals and clinics instructing their staff on procedures to follow. In addition, we based some decisions on data collected by agencies such as the CDC, FDA, IHME, ISDA, and Worldometer. None of the case studies or cohort studies used a large number of participants. The largest group of participants numbered less than 500 and some case studies had fewer than 30 patients. However, the review of the literature revealed the need for individualized treatment protocols due to the variability of patient clinical presentation and survivability. A number of factors appear to influence mortality: the stage at which the patient first presented for care, pre-existing health conditions, age, and the viral load the patient carried. Conclusion and Relevance: COVID-19 can be divided into three distinct Stages, beginning at the time of infection (Stage I), sometimes progressing to pulmonary involvement (Stage II, with or without hypoxemia) and less frequently to systemic inflammation (Stage III). In addition to modeling the stages of disease progression, we have also created a treatment algorithm which considers age, comorbidities, clinical presentation, and disease progression to suggest drug classes or treatment modalities. This paper presents the first evidence-based recommendations for individualized treatment for COVID-19.

negative: Anti COVID-19 Drugs: Need for More Clinical Evidence and Global Action The World Health Organization (WHO) called the outbreak of coronavirus infectious disease-2019 (COVID-19) a “Public Health Emergency of International Concern” (PHEIC). According to the WHO, Centers for Disease Control and Prevention (CDC), and the US Food and Drug Administration (FDA), currently there are no medicines or vaccines that have been claimed to be useful in the prevention or treatment of COVID-19. Several existing antiviral drugs, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), human immunodeficiency virus (HIV), and malaria, are being investigated as COVID-19 treatments and some of them are being used in clinical trials. According to the CDC and Chinese treatment guidelines for COVID-19, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and one of the investigational agents (remdesivir) are recommended in critically ill older patients. The use of other potential drugs reported in different studies may be considered if treatment with first-line drugs is ineffective. There are currently no complete data available from large randomized clinical trials (RCTs) to provide clinical guidance on the use, dosing, or duration to validate the effective role, safety profile, and adverse effects of all of the trial drugs for prophylaxis or treatment of COVID-19. Until now, it is still unclear which drug can successfully fight against the disease. Therefore, for the better safety of patients with COVID-19, further clinical trials and large randomized controlled studies are needed to validate the effective role, safety profile, and adverse effects of all the potential drugs. Such a measure requires action at the global level.

negative: AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus induces protective antibodies in cotton rats Abstract Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants, and no vaccine is available. In this report, recombinant AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive neutralizing antibodies against RSV subgroups A and B were detected in cotton rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton rats infected with RSV, RSV was recovered and lung histopathological finding was compatible with interstitial pneumonia, demonstrating thickening of alveolar walls and infiltration of mononuclear cells. When cotton rats immunized with MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was recovered and very mild inflammation was noted without RSV antigen expression. When they were challenged with subgroup B, protective efficacy decreased. When cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low levels of infectious virus were recovered from lung. When challenged with subgroup B, no protective effects was demonstrated, demonstrating large amounts of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate and protective effects should be confirmed in monkey model.

negative: Statistical Issues and Lessons Learned from COVID-19 Clinical Trials with Lopinavir-Ritonavir and Remdesivir Background: Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in December 2019, it has rapidly spread in more than 200 countries or territories with over 8 million confirmed cases and 440,000 deaths by June 17, 2020. Recently, three randomized clinical trials on COVID-19 treatments were completed, one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. However, several statistical issues in the original design and analysis of the three trials are identified, which might shed doubts on their findings and the conclusions should be evaluated with cautions. Objective: From statistical perspectives, we identify several issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. Methods: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al. failed to reach the planned sample size due to a lack of eligible patients, while the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) in this context to analyze the reconstructed data due to the existence of death as competing risk and a terminal event. The remdesivir trial of Beigel et al. reported the median recovery time of the remdesivir and placebo groups and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We reanalyzed the data to report other percentiles of the time to recovery and adopted the bootstrap method and permutation test to construct the confidence intervals as well as the P values. The restricted mean time to recovery (RMTR) was also computed as a global and robust measure for efficacy. Results: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of terminal rates was -8.74% (95% CI [-21.04, 3.55]; P=.16) and the hazards ratio (HR) adjusted for terminal rates was 1.05 (95% CI [0.78, 1.42]; P=.74), indicating no significant difference. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI [-3.62, 0.28]; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al., the difference of terminal rates was -0.89% (95% CI [-2.84, 1.06]; P=.19) and the HR adjusted for terminal rates was 0.92 (95% CI [0.63, 1.35]; P=.67). The difference of RMTIs at day 28 was -0.89 day (95% CI [-2.84, 1.06]; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the HR estimates would reach statistical significance if the target sample size had been maintained, and both conditional and unconditional prediction delivered significant HR results if the trial had continued to double the target sample size. For the remdesivir trial of Beigel et al., the difference of RMTRs between the remdesivir and placebo groups up to day 30 was -2.7 days (95% CI [-4.0, -1.2]; P<.001), confirming the superiority of remdesivir. The difference in recovery time at the 25th percentile (95% CI [-3, 0]; P=.65) was insignificant, while the differences manifested to be statistically significant at larger percentiles. Conclusions: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis for ongoing and future COVID-19 trials.

negative: COVID-19: Wait for a novel drug or act with the age old drug - Do we have a choice?

negative: Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren’s syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still’s disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.

negative: Psychological consequences of the Flint Water Crisis: A systematic review. Given the COVID-19 outbreak, these unprecedented times pose many urgent dilemmas about how to support the mental health of communities. The goal of this research is to summarize existing literature on the mental health impact of the recent Flint Water Crisis. In March 2020, we searched five databases for literature exploring the psychological consequences of the crisis. Main findings were extracted. 132 citations were screened and eleven included in the review. Results suggest a negative psychological effect caused by the water crisis, including anxiety and health worries, exacerbated by lowered trust in public health officials, uncertainty about the long-term impacts of the crisis, financial hardships, stigma, and difficulties seeking help. There was evidence that concerns about tap water continued even after the state of emergency was lifted. With a possible compounded effect to residents of Flint with the recent COVID-19 pandemic, the results highlight the need for more resources for psychological health interventions in Flint as well as a need for local governments and health authorities to regain the trust of those affected by the Flint Water Crisis.

negative: Epidemiology of CoVID-19 and predictors of recovery in the Republic of Korea Background: The recent CoVID-19 pandemic has emerged as a threat to global health. Though current evidence on the epidemiology of the disease is emerging, very little is known about the predictors of recovery. We describe the epidemiology of confirmed CoVID-19 patients in Republic of Korea and identify predictors of recovery. Materials and methods: Using publicly available data for confirmed CoVID-19 cases from the Korea Centers for Disease Control and Prevention from January 20, 2020 to April 30, 2020, we undertook descriptive analyses of cases stratified by sex, age group, place of exposure, date of confirmation and province. Correlation was tested among all predictors (sex, age group, place of exposure and province) with the Pearsons correlation coefficient. Associations between recovery from CoVID-19 and predictors were estimated using a multivariable logistic regression model. Results: Majority of the confirmed cases were females (56 percent), from 20-29 age group (24.3 percent), and primarily from three provinces Gyeongsangbuk (36.9 percent), Gyeonggi (20.5 percent) and Seoul (17.1 percent). Case fatality ratio was 2.1 percent and 41.6 percent cases recovered. Older patients, patients from certain provinces such as Daegu, Gyeonggi, Gyeongsangbuk, Jeju, Jeollabuk and Jeollanam, and those contracting the disease from healthcare settings had lower recovery. Conclusions: Our study adds to the very limited evidence base on potential predictors of recovery among confirmed CoVID-19 cases. We call additional research to explore the predictors of recovery and support development of policies to protect the vulnerable patient groups.

negative: Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy Abstract The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.

negative: Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients Summary Purpose The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. Participants and methods A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. Results Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan–Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. Conclusion Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases.

negative: Susceptibility of human and rat neural cell lines to infection by SARS-coronavirus Abstract Pathological characterization of autopsied tissues from patients with SARS revealed severe damage in restricted tissues, such as lung, with no apparent cell damage in other tissues, such as intestine and brain. Here, we examined the susceptibility of neural cell lines of human (OL) and rat (C6) origins to SARS-associated coronavirus. Both of the neural cell lines showed no apparent cytopathic effects (CPE) by infection but produced virus with infectivity of 102–5 per ml, in sharp contrast to the production by infected Vero E6 cells of >109 per ml that showed a lytic infection with characteristic rounding CPE. Interestingly, the infection of intestinal cell line CaCo-2 also induced no apparent CPE, with production of the virus at a slightly lower level as that of the Vero E6 cell culture. Notably, the cellular receptor for the virus, angiotensin-converting enzyme 2 was expressed at similar levels on Vero E6 and CaCo-2 cells, but at undetectable levels on OL and C6 cells.

negative: Burn injury Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient. Accordingly, patients with burn injury cannot be considered recovered when the wounds have healed; instead, burn injury leads to long-term profound alterations that must be addressed to optimize quality of life. Burn care providers are, therefore, faced with a plethora of challenges including acute and critical care management, long-term care and rehabilitation. The aim of this Primer is not only to give an overview and update about burn care, but also to raise awareness of the ongoing challenges and stigmata associated with burn injuries.

negative: Determination of SARS‐coronavirus by a microfluidic chip system We have developed a new experimental system based on a microfluidic chip to determine severe acute respiratory syndrome coronavirus (SARS‐CoV). The system includes a laser‐induced fluorescence microfluidic chip analyzer, a glass microchip for both polymerase chain reaction (PCR) and capillary electrophoresis, a chip thermal cycler based on dual Peltier thermoelectric elements, a reverse transcription‐polymerase chain reaction (RT‐PCR) SARS diagnostic kit, and a DNA electrophoretic sizing kit. The system allows efficient cDNA amplification of SARS‐CoV followed by electrophoretic sizing and detection on the same chip. To enhance the reliability of RT‐PCR on SARS‐CoV detection, duplex PCR was developed on the microchip. The assay was carried out on a home‐made microfluidic chip system. The positive and the negative control were cDNA fragments of SARS‐CoV and parainfluenza virus, respectively. The test results showed that 17 positive samples were obtained among 18 samples of nasopharyngeal swabs from clinically diagnosed SARS patients. However, 12 positive results from the same 18 samples were obtained by the conventional RT‐PCR with agarose gel electrophoresis detection. The SARS virus species can be analyzed with high positive rate and rapidity on the microfluidic chip system.

negative: Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019 OBJECTIVES: Coronavirus disease 2019 has emerged as a major global health threat with a great number of deaths in China. We aimed to assess the association between Acute Physiology and Chronic Health Evaluation II score and hospital mortality in patients with coronavirus disease 2019, and to compare the predictive ability of Acute Physiology and Chronic Health Evaluation II score, with Sequential Organ Failure Assessment score and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65) score. DESIGN: Retrospective observational cohort. SETTING: Tongji Hospital in Wuhan, China. SUBJECTS: Confirmed patients with coronavirus disease 2019 hospitalized in the ICU of Tongji hospital from January 10, 2020, to February 10, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 178 potentially eligible patients with symptoms of coronavirus disease 2019, 23 patients (12.92%) were diagnosed as suspected cases, and one patient (0.56%) suffered from cardiac arrest immediately after admission. Ultimately, 154 patients were enrolled in the analysis and 52 patients (33.77%) died. Mean Acute Physiology and Chronic Health Evaluation II score (23.23 ± 6.05) was much higher in deaths compared with the mean Acute Physiology and Chronic Health Evaluation II score of 10.87 ± 4.40 in survivors (p < 0.001). Acute Physiology and Chronic Health Evaluation II score was independently associated with hospital mortality (adjusted hazard ratio, 1.07; 95% CI, 1.01–1.13). In predicting hospital mortality, Acute Physiology and Chronic Health Evaluation II score demonstrated better discriminative ability (area under the curve, 0.966; 95% CI, 0.942–0.990) than Sequential Organ Failure Assessment score (area under the curve, 0.867; 95% CI, 0.808–0.926) and CURB65 score (area under the curve, 0.844; 95% CI, 0.784–0.905). Based on the cut-off value of 17, Acute Physiology and Chronic Health Evaluation II score could predict the death of patients with coronavirus disease 2019 with a sensitivity of 96.15% and a specificity of 86.27%. Kaplan-Meier analysis showed that the survivor probability of patients with coronavirus disease 2019 with Acute Physiology and Chronic Health Evaluation II score less than 17 was notably higher than that of patients with Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 (p < 0.001). CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score was an effective clinical tool to predict hospital mortality in patients with coronavirus disease 2019 compared with Sequential Organ Failure Assessment score and CURB65 score. Acute Physiology and Chronic Health Evaluation II score greater than or equal to 17 serves as an early warning indicator of death and may provide guidance to make further clinical decisions.

negative: History of coronary heart disease increases the mortality rate of COVID-19 patients: a nested case-control study Background: China has experienced an outbreak of a novel human coronavirus (SARS-CoV-2) since December 2019, which quickly became a worldwide pandemic in early 2020. There is limited evidence on the mortality risk effect of pre-existing comorbidities for coronavirus disease 2019 (COVID-19), which has important implications for early treatment. Objective: Evaluate the risk of pre-existing comorbidities on COVID-19 mortality, and provide clinical suggestions accordingly. Method: This study used a nested case-control design. A total of 94 publicly reported deaths in locations outside of Hubei Province, China, between December 18th, 2019 and March 8th, 2020 were included as cases. Each case was matched with up to three controls, based on gender and age (94 cases and 181 controls). The inverse-probability-weighted Cox proportional hazard model was performed. Results: History of comorbidities significantly increased the death risk of COVID-19: one additional pre-existing comorbidity led to an estimated 40% higher risk of death (p<0.001). The estimated mortality risk in patients with CHD was three times of those without CHD (p<0.001). The estimated 30-day survival probability for a profile patient with pre-existing CHD (65-year-old female with no other comorbidities) was 0.53 (95% CI [0.34-0.82]), while it was 0.85 (95% CI [0.79-0.91]) for those without CHD. Older age was also associated with increased death risk: every 5-year increase in age was associated with a 20% increased risk of mortality (p<0.001). Conclusion: Extra care and early medical intervention are needed for patients with pre-existing comorbidities, especially CHD.

negative: Statistical methods for estimating cure fraction of COVID-19 patients in India The human race is under the COVID-19 pandemic menace since beginning of the year 2020. Even though the disease is easily transmissible, a massive fraction of the affected people are recovering. Most of the recovered patients will not experience death due to COVID-19, even if they observed for a long period. They can be treated as long term survivors (cured population) in the context of lifetime data analysis. In this article, we present some statistical methods to estimate the cure fraction of the COVID-19 patients in India. Proportional hazards mixture cure model is used to estimate the cure fraction and the effect of covariates gender and age on lifetime. The data available on website https://api.cvoid19india.org is used in this study. We can see that, the cure fraction of the COVID-19 patients in India is more than 90%, which is indeed an optimistic information.

negative: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India Abstract Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.

negative: Pandemic (H1N1) 2009 Influenza Community Transmission Was Established in One Australian State When the Virus Was First Identified in North America BACKGROUND: In mid-June 2009 the State of Victoria in Australia appeared to have the highest notification rate of pandemic (H1N1) 2009 influenza in the world. We hypothesise that this was because community transmission of pandemic influenza was already well established in Victoria at the time testing for the novel virus commenced. In contrast, this was not true for the pandemic in other parts of Australia, including Western Australia (WA). METHODS: We used data from detailed case follow-up of patients with confirmed infection in Victoria and WA to demonstrate the difference in the pandemic curve in two Australian states on opposite sides of the continent. We modelled the pandemic in both states, using a susceptible-infected-removed model with Bayesian inference accounting for imported cases. RESULTS: Epidemic transmission occurred earlier in Victoria and later in WA. Only 5% of the first 100 Victorian cases were not locally acquired and three of these were brothers in one family. By contrast, 53% of the first 102 cases in WA were associated with importation from Victoria. Using plausible model input data, estimation of the effective reproductive number for the Victorian epidemic required us to invoke an earlier date for commencement of transmission to explain the observed data. This was not required in modelling the epidemic in WA. CONCLUSION: Strong circumstantial evidence, supported by modelling, suggests community transmission of pandemic influenza was well established in Victoria, but not in WA, at the time testing for the novel virus commenced in Australia. The virus is likely to have entered Victoria and already become established around the time it was first identified in the US and Mexico.

negative: Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1 -19) during pregnancy: a systematic review and meta-analysis ABSTRACT Objective The aim of this systematic review was to report pregnancy and perinatal outcomes of Coronavirus (CoV) spectrum infections, and particularly COVID-19 disease due to SARS-COV-2 infection during pregnancy. Data sources Medline, Embase, Cinahl and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for “coronavirus” or “severe acute respiratory syndrome” or “SARS” or “Middle East respiratory syndrome” or “MERS” or “COVID-19” and “pregnancy”. The search and selection criteria were restricted to English language. Study eligibility criteria Inclusion criteria were pregnant women with a confirmed Coronavirus related illness, defined as either SARS, MERS or COVID-19. Study appraisal and synthesis methods We used meta-analyses of proportions to combine data and reported pooled proportions. The pregnancy outcomes observed included miscarriage, preterm birth, pre-eclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score < 7 at five minutes, neonatal asphyxia, admission to neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results 19 studies including 79 women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8% and the most common symptoms were fever (82.6%), cough (57.1%) and dyspnea (27.0%). For all CoV infections, the rate of miscarriage was 39.1% (95% CI 20.2-59.8); the rate of preterm birth < 37 weeks was 24.3% (95% CI 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (95% CI 9.5-34.9), preeclampsia in 16.2% (95% CI 4.2-34.1), and fetal growth restriction in 11.7% (95% CI 3.2-24.4); 84% were delivered by cesarean; the rate of perinatal death was 11.1% (95% CI 84.8-19.6) and 57.2% (95% CI 3.6-99.8) of newborns were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth < 37 weeks, occurring in 41.1% (95% CI 25.6-57.6) of cases, while the rate of perinatal death was 7.0% (95% CI 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion In mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, PTB is the most common adverse pregnancy outcome. Miscarriage, preeclampsia, cesarean, and perinatal death (7-11%) were also more common than in the general population. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy.

negative: Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury. Arterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets.

negative: Comprehensive detection and identification of human coronaviruses, including the SARS-associated coronavirus, with a single RT-PCR assay Abstract The SARS-associated human coronavirus (SARS-HCoV) is a newly described, emerging virus conclusively established as the etiologic agent of the severe acute respiratory syndrome (SARS). This study presents a single-tube RT-PCR assay that can detect with high analytical sensitivity the SARS-HCoV, as well as several other coronaviruses including other known human respiratory coronaviruses (HCoV-OC43 and HCoV-229E). Species identification is provided by sequencing the amplicon, although a rapid screening test by restriction enzyme analysis has proved to be very useful for the analysis of samples obtained during the SARS outbreak in Toronto, Canada.

negative: Grief During the COVID-19 Pandemic: Considerations for Palliative Care Providers Abstract The COVID-19 pandemic is anticipated to continue spreading widely across the globe throughout 2020. To mitigate the devastating impact of COVID-19, social distancing and visitor restrictions in healthcare facilities have been widely implemented. Such policies and practices, along with the direct impact of the spread of COVID-19, complicate issues of grief that are relevant to medical providers. We describe the relationship of the COVID-19 pandemic to anticipatory grief, disenfranchised grief, and complicated grief for individuals, families, and their providers. Further, we provide discussion regarding countering this grief through communication, advance care planning, and self-care practices. We provide resources for healthcare providers, in addition to calling on palliative care providers to consider their own role as a resource to other specialties during this public health emergency.

negative: Searching for a coronavirus cure in the blood The blood of people who have recovered from COVID-19 may be the world’s most sought-after substance right now It contains a stockpile of antibodies made by immune cells that have successfully mounted an attack on the invading virus, SARS-CoV-2 While multiple efforts are focusing on repurposing existing drugs, like remdesivir or chloroquine, to fight this new virus, many scientists think that the fastest route to novel therapies specifically designed to treat the infection could come by harvesting those antibodies These antibody-based therapies could take many forms The simplest, and the only that is already being tested in people with COVID-19, is convalescent plasma, the antibody-rich portion of blood donated from someone who recovered from the disease At the other end of the spectrum, companies are meticulously analyzing plasma from recovered humans or immunized animals to select the very best antibodies, which they can use to manufacture traditional monoclonal antibody therapies These approaches, and others in between, are barreling toward the clinic at a pandemic pace

negative: Coronavirus Disease 2019 (COVID-19) Pneumonia in a Hemodialysis Patient Coronavirus disease 2019 (COVID-19) is a highly infective disease caused by the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2). Previous studies of the COVID-19 pneumonia outbreak were based on information from the general population. Limited data are available for hemodialysis patients with COVID-19 pneumonia. This report describes the clinical characteristics of COVID-19 in an in-center hemodialysis patient, as well as our experience in implementing steps to prevent the spread of COVID-19 pneumonia among in-center hemodialysis patients. The diagnosis, infection control, and treatment of COVID-19 in hemodialysis patients are discussed in this report, and we conclude with recommendations for how a dialysis facility can respond to COVID-19 based on our experiences.

negative: Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease BACKGROUND: Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3–5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. METHODS: Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. RESULTS: In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. CONCLUSIONS: Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event.

negative: Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.

negative: Potential Effects of Coronaviruses on the Cardiovascular System: A Review Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system. Observations: Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality. Conclusions and Relevance: Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.

negative: Clinical Characteristics and Differential Clinical Diagnosis of Novel Coronavirus Disease 2019 (COVID-19) Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several nations. It is of serious concern and extreme challenge not only to the health personnel but also to the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme (hACE-2) receptor and causes constitutional and respiratory symptoms. The major mode of transmission is human to human and the median incubation period is 4 days. The most common symptom as studied from various cohorts of COVID-19 patients are fever (83–98%) followed by fatigue (70%) and dry cough (59%); gastrointestinal symptoms are relatively uncommon differentiating it from SARS and MERS. Most of the SAR-CoV-2 infection are mild (80%) with a usual recovery period of 2 weeks. COVID-19 commonly affects males in the middle age and elderly age group, with highest case fatality (8–15%) among those aged >80 years. The disease begins with fever, dry cough, fatigue and myalgia progressing to dyspnoea and ARDS over 6 and 8 days post exposure, respectively. Underlying co-morbidities increase mortality in COVID-19. Poor prognostic factors are elderly, co-morbidities, severe lymphopaenia, high CRP and D-dimer >1 μg/L. The overall mortality rate ranges from 1.5 to 3.6%. COVID-19 has to be differentiated from other viral and bacterial pneumonias as they are more common among healthy adults. Despite constant and vigorous efforts by researchers and health agencies, we are far from containment, cure or prevention by vaccine; hence right information and stringent prevention and control measures are the only weapon in the armoury to combat the ongoing infection.

negative: The Economic Impact of the COVID-19 Pandemic on Radiology Practices The COVID-19 pandemic will have a profound impact on Radiology practices across the country. Policy measures adopted to slow the transmission of disease are decreasing the demand for imaging independent of COVID-19. Hospital preparations to expand crisis capacity are further diminishing the amount of appropriate medical imaging that can be safely performed. While economic recessions generally tend to result in decreased health care expenditures, radiology groups have never experienced an economic shock that is simultaneously exacerbated by the need to restrict the availability of imaging. Outpatient heavy practices will feel the biggest impact of these changes, but all imaging volumes will decrease. Anecdotal experience suggests that radiology practices should anticipate 50%-70% decreases in imaging volume that will last a minimum of 3-4 months, depending on the location of practice and the severity of the COVID-19 pandemic in each region. The CARES Act provides multiple means of direct and indirect aid to healthcare providers and small businesses. The final allocation of this funding is not yet clear, and it is likely that additional congressional action will be necessary to stabilize health care markets. Administrators and practice leaders need to be proactive with practice modifications and financial maneuvers that can position them to emerge from this pandemic in the most viable economic position. It is possible that this crisis will have lasting effects on the structure of the radiology field.

negative: Effects of humidity and other factors on the generation and sampling of a coronavirus aerosol Suspensions of transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were nebulized at rates of 0.1–0.2 ml/min into moving air using a Collison nebulizer or a plastic medical nebulizer operating at pressures ranging from 7 to 15 psi. The airborne viruses were collected on heating, ventilating, and air conditioning (HVAC) filters in an experimental apparatus and also sampled upstream of these test filters using AGI-30 and BioSampler impinger samplers. To study the effects of relative humidity (RH) on TGEV collection by the filters and samplers, the virus was nebulized into air at 30, 50, 70, and 90% RH. There were no significant changes in virus titer in the nebulizer suspension before and after nebulization for either nebulizer at any of the pressures utilized. Aerosolization efficiency – the ratio of viable virus sampled with impingers to the quantity of viable virus nebulized – decreased with increasing humidity. BioSamplers detected more airborne virus than AGI-30 samplers at all RH levels. This difference was statistically significant at 30 and 50% RH. Nebulizer type and pressure did not significantly affect the viability of the airborne virus. Virus recovery from test filters relative to the concentration of virus in the nebulizer suspension was less than 10%. The most and the least virus were recovered from filter media at 30% and 90% RH, respectively. The results suggest that TGEV, and perhaps other coronaviruses, remain viable longer in an airborne state and are sampled more effectively at low RH than at high humidity.

negative: An Italian multicenter retrospective-prospective observational study on neurological manifestations of COVID-19 (NEUROCOVID) Neurological manifestations of COVID-19 have been described in both single case reports and retrospective scanty case series. They may be linked to the potential neurotropism of the SARS-COV-2 virus, as previously demonstrated for other coronaviruses. We report here the description of a multicenter retrospective-prospective observational study promoted by the Italian Society of Neurology (SIN), involving the Italian Neurological Departments, who will consecutively recruit patients with neurological symptoms and/or signs, occurred at the onset or as a complication of COVID-19. Hospitalized patients will be recruited either in neurological wards or in COVID wards; in the latter cases, they will be referred from other specialists to participant neurologists. Outpatients with clinical signs of COVID and neurological manifestations will be also referred to participating neurologists from primary care physicians. A comprehensive data collection, in the form of electronic case report form (eCRF), will register all possible neurological manifestations involving central nervous systems, peripheral nerves, and muscles, together with clinical, laboratory (including cerebrospinal fluid, if available), imaging, neurological, neurophysiological, and neuropsychological data. A follow-up at hospital discharge (in hospitalized patients), and for all patients after 3 and 6 months, is also planned. We believe that this study may help to intercept the full spectrum of neurological manifestations of COVID-19 and, given the large diffusion at national level, can provide a large cohort of patients available for future more focused investigations. Similar observational studies might also be proposed at international level to better define the neurological involvement of COVID-19.

negative: COVID-19 and diabetes mellitus: what we know, how our patients should be treated now, and what should happen next

negative: A Diabetic Patient With 2019-nCoV (COVID-19) Infection Who Recovered and Was Discharged From Hospital Novel coronavirus has become a global health hazard and its high infectivity is alarming. The imaging findings of the 2019-nCoV infection in our young diabetic patient featured ground-glass opacities and consolidations in both lungs. The lung lesions may involute rapidly during the course. The patient showed improvement both clinically and on computed tomography imaging at discharged after 2 weeks’ treatment. Computed tomography scans of patients helped monitor the changes continuously, which could timely provide the information of the evolution of the disease or therapeutic effect to clinicians.

negative: Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

negative: Nervous system damage after COVID-19 infection: Presence or absence?

negative: COVID-19 Infection in a Patient with End-Stage Kidney Disease Since December 2019, the epidemic of coronavirus disease 2019 (COVID-19) has spread very rapidly in China and worldwide. In this article, we report on a 75-year-old man infected with 2019 novel coronavirus who has end-stage kidney disease (ESKD). COVID-19 patients with ESKD need isolation dialysis, but most of them cannot be handled in time due to limited continuous renal replacement therapy (CRRT) machines. CRRT provided benefits for this patient by removing potentially damaging toxins and stabilizing his metabolic and hemodynamic status. With the control of uremia and fluid status, this patient ended up with an uneventful post-CRRT course, absence of clinical symptoms, and negative PCR tests. Greater efforts are needed to decrease the mortality of COVID-19-infected ESKD patients.

negative: 2019 Novel Coronavirus Disease (COVID-19): Paving the Road for Rapid Detection and Point-of-Care Diagnostics We believe a point-of-care (PoC) device for the rapid detection of the 2019 novel Coronavirus (SARS-CoV-2) is crucial and urgently needed. With this perspective, we give suggestions regarding a potential candidate for the rapid detection of the coronavirus disease 2019 (COVID-19), as well as factors for the preparedness and response to the outbreak of the COVID-19.

negative: Three children who recovered from novel coronavirus 2019 pneumonia

negative: Molecular pathology of emerging coronavirus infections Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.

negative: Estimating the cure rate and case fatality rate of the ongoing epidemic COVID-19 The epidemic caused by the novel coronavirus COVID-19 in Wuhan at the end of 2019 has become an urgent public event of worldwide concern. However, due to the changing data of the epidemic, there is no scientific estimate of the cure rate and case fatality rate of the epidemic. This study proposes a method to estimate the cure rate and case fatality rate of COVID-19. The ratio of cumulative discharges on a given day to the sum of cumulative discharges on a given day and cumulative deaths before j days is used to estimate the cure rate. Moreover, the case fatality ratio can also be estimated. After simulation calculations, j is statistically appropriate when it is 8-10, and it is also clinically appropriate. When j is 9, based on the available data, it is inferred that the cure rate of this epidemic is about 93% and the case fatality rate is about 7%. This method of estimating the cure rate can be used to evaluate the effectiveness of treatment in different medical schemes and different regions, and has great value and significance for decision-making in the epidemic.

negative: ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection The COVID-19 pandemics is posing unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Patients with worst outcomes and higher mortality are reported to include immunocompromised subjects, namely older adults and polymorbid individuals and malnourished people in general. ICU stay, polymorbidity and older age are all commonly associated with high risk for malnutrition, representing per se a relevant risk factor for higher morbidity and mortality in chronic and acute disease. Also importantly, prolonged ICU stays are reported to be required for COVID-19 patients stabilization, and longer ICU stay may per se directly worsen or cause malnutrition, with severe loss of skeletal muscle mass and function which may lead to disability, poor quality of life and additional morbidity. Prevention, diagnosis and treatment of malnutrition should therefore be routinely included in the management of COVID-19 patients. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing concise guidance for nutritional management of COVID-19 patients by proposing 10 practical recommendations. The practical guidance is focused to those in the ICU setting or in the presence of older age and polymorbidity, which are independently associated with malnutrition and its negative impact on patient survival.

negative: The intrinsic vulnerability of networks to epidemics Contact networks are convenient models to investigate epidemics, with nodes and links representing potential hosts and infection pathways, respectively. The outcomes of outbreak simulations on networks are driven both by the underlying epidemic model, and by the networks’ structural properties, so that the same pathogen can generate different epidemic dynamics on different networks. Here we ask whether there are general properties that make a contact network intrinsically vulnerable to epidemics (that is, regardless of specific epidemiological parameters). By conducting simulations on a large set of modelled networks, we show that, when a broad range of network topologies is taken into account, the effect of specific network properties on outbreak magnitude is stronger than that of fundamental pathogen features such as transmission rate, infection duration, and immunization ability. Then, by focusing on a large set of real world networks of the same type (potential contacts between field voles, Microtus agrestis), we showed how network structure can be used to accurately assess the relative, intrinsic vulnerability of networks towards a specific pathogen, even when those have limited topological variability. These results have profound implications for how we prevent disease outbreaks; in many real world situations, the topology of host contact networks can be described and used to infer intrinsic vulnerability. Such an approach can increase preparedness and inform preventive measures against emerging diseases for which limited epidemiological information is available, enabling the identification of priority targets before an epidemic event.

negative: Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) Importance: Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. Objective: To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. Design, Setting, and Participants: This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. Main Outcomes and Measures: Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. Result: Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (ß = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (ß = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168). Conclusions and Relevance: Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.

negative: Effectiveness of Testing, Tracing, Social Distancing and Hygiene in Tackling Covid-19 in India: A System Dynamics Model We present a System Dynamics (SD) model of the Covid-19 pandemic spread in India. The detailed age-structured compartment-based model endogenously captures various disease transmission pathways, expanding significantly from the standard SEIR model. The model is customized for India by using the appropriate population pyramid, contact rate matrices, external arrivals (as per actual data), and a few other calibrated fractions based on the reported cases of Covid-19 in India. Also, we have explicitly modeled, using independent time-variant levers, the effects of testing, contact tracing, isolating Covid-positive patients, quarantining, use of mask/better hygiene practices, social distancing through contact rate reductions at distinct zones of home(H), work(W), school(S) and other(O) locations. Simulation results show that, even after an extended lock-down, some non-trivial number of infections (even asymptomatic) will be left and the pandemic will resurface. Only tools that work against the pandemic is high rate of testing of those who show Covid-19 like symptoms, isolating them if they are positive and contact tracing all contacts of positive patients and quarantining them, in combination with use of face masks and personal hygiene. A wide range of combination of effectiveness of contact tracing, isolation, quarantining and personal hygiene measures help minimize the pandemic impact and some imperfections in implementation of one measure can be compensated by better implementation of other measures.

negative: The fate of house cats during the COVID-19 pandemic

negative: Hitting the reset button for hospitality research in times of crisis: Covid19 and beyond

negative: Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.

negative: Clinical Characteristics and Outcomes of 421 Patients With COVID-19 Treated in a Mobile Cabin Hospital BACKGROUND: In December 2019, a novel coronavirus-associated pneumonia, now known as coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. RESEARCH QUESTION: It is unknown whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms. STUDY DESIGN AND METHODS: This study retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9, 2020, to March 5, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. RESULTS: Of the patients who were discharged from the cabin hospital, 362 (86.0%) were categorized as recovered; 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%); 5.2% exhibited no obvious symptoms. High fever (> 39.0°C) was more common in severe cases than in recovered cases (18.6% vs 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in patients with severe disease (66.1%) than in those who recovered (31.8%, P < .0001). The median length of hospitalization was 17 days (interquartile range, 14-19 days), and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 days (interquartile range, 6-10 days). INTERPRETATION: Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms and offer an effective isolation area to prevent the spread of severe acute respiratory syndrome coronavirus 2.

negative: An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses. The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed.

negative: The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control Non-pharmaceutical interventions to combat COVID-19 transmission have worked to slow the spread of the epidemic but can have high socio-economic costs. It is critical we understand the efficacy of non-pharmaceutical interventions to choose a safe exit strategy. Many current models are not suitable for assessing exit strategies because they do not account for epidemic resurgence when social distancing ends prematurely (e.g., statistical curve fits) nor permit scenario exploration in specific locations. We developed an SEIR-type mechanistic epidemiological model of COVID-19 dynamics to explore temporally variable non-pharmaceutical interventions. We provide an interactive tool and code to estimate the transmission parameter, β, and the effective reproduction number, [Formula: see text]. We fit the model to Santa Clara County, California, where an early epidemic start date and early shelter-in-place orders could provide a model for other regions. As of April 22, 2020, we estimate an R(E) of 0.982 (95% CI: 0.849 – 1.107) in Santa Clara County. After June 1 (the end-date for Santa Clara County shelter-in-place as of April 27), we estimate a shift to partial social distancing, combined with rigorous testing and isolation of symptomatic individuals, is a viable alternative to indefinitely maintaining shelter-in-place. We also estimate that if Santa Clara County had waited one week longer before issuing shelter-in-place orders, 95 additional people would have died by April 22 (95% CI: 7 – 283). Given early life-saving shelter-in-place orders in Santa Clara County, longer-term moderate social distancing and testing and isolation of symptomatic individuals have the potential to contain the size and toll of the COVID-19 pandemic in Santa Clara County, and may be effective in other locations.

negative: Replication of a bovine coronavirus in organ cultures of foetal trachea Abstract A strain of bovine coronavirus (BC) adapted to tissue culture, was inoculated into organ cultures of bovine foetal trachea. Haemagglutinin in the fluid from infected organ cultures reached titres of 32 and characteristic coronavirus particles were observed electron microscopically. BC virus antigen was detected in frozen sections of the organ cultures by staining with fluorescent antibody. These data were evidence that BC virus replicated in organ cultures of respiratory tissue. The use of this technique for primary isolation of bovine coronaviruses from field material is discussed.

negative: ANALYSIS OF CLINICAL RECOVERY-PERIOD AND RECOVERY RATE ESTIMATION OF THE FIRST 1000 COVID-19 PATIENTS IN SINGAPORE COVID-19 has been declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. In this paper, we investigate various aspects of the clinical recovery of the first 1000 COVID-19 patients in Singapore, spanning from January 23 to April 01, 2020. This data consists of 245 clinically recovered patients. The first part of the paper studies the descriptive statistics and the influence of demographic parameters, namely age and gender, in the clinical recovery-period of COVID-19 patients. The second part of the paper is on identifying the distribution of the length of the recovery-period for the patients. We identify a piecewise analysis of three different periods, identified based on trends of both positive confirmation and clinical recovery of COVID-19. As expected, the overall recovery rate has reduced drastically during the exponential increase of incidences. However, our in-depth analysis shows that there is a shift in the age-group of incidences to the younger population, and the recovery-period of the younger population is considerably lower. Here, we have estimated the recovery rate to be 0.125. Overall, the prognosis of COVID-19 indicates an improvement in recovery rate owing to the government-mandated practices of restricted mobility of the older population and aggressive contact tracing.

negative: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic BACKGROUND: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. METHODS: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I(2) statistics, and assessment of study quality. FINDINGS: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5–36·0] of 129 patients), depressed mood (42 [32·6%; 24·7–40·9] of 129), anxiety (46 [35·7%; 27·6–44·2] of 129), impaired memory (44 [34·1%; 26·2–42·5] of 129), and insomnia (54 [41·9%; 22·5–50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5–14·1] of 332 patients), insomnia (34 [12·1%; 8·6–16·3] of 280), anxiety (21 [12·3%; 7·7–17·7] of 171), irritability (28 [12·8%; 8·7–17·6] of 218), memory impairment (44 [18·9%; 14·1–24·2] of 233), fatigue (61 [19·3%; 15·1–23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9–37·3] of 181) and sleep disorder (14 [100·0%; 88·0–100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. INTERPRETATION: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. FUNDING: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

negative: Absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from MERS in South Korea We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection.

negative: Tracheostomy in patients with acute respiratory distress syndrome is not related to quality of life, symptoms of psychiatric disorders or return-to-work: the prospective DACAPO cohort study BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors. METHODS: Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive–compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models. RESULTS: Primary 877 ARDS patients (mean ± standard deviation: 54 ± 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: − 0.73 [− 3.96, 2.51]; MCS-12: − 0.71 [− 4.92, 3.49]), symptoms of psychiatric disorders (depression: 0.10 [− 1.43, 1.64]; PTSD: 3.31 [− 1.81, 8.43]; anxiety: 1.26 [0.41, 3.86]; obsessive–compulsive disorder: 0.59 [0.05, 6.68]) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI]). CONCLUSIONS: Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered)

negative: Pulmonary Rehabilitation for Patients with Coronavirus Disease 2019 (COVID-19) As a highly infectious respiratory tract disease, coronavirus disease 2019 (COVID-19) can cause respiratory, physical, and psychological dysfunction in patients. Therefore, pulmonary rehabilitation is crucial for both admitted and discharged patients of COVID-19. In this study, based on the newly released pulmonary rehabilitation guidelines for patients with COVID-19, as well as evidence from the pulmonary rehabilitation of patients with severe acute respiratory syndrome, we investigated pulmonary rehabilitation for patients with COVID-19 having complications, such as chronic pulmonary disease, and established an intelligent respiratory rehabilitation model for these patients.

negative: Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer Abstract There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

negative: Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

negative: Placental transfer and safety in pregnancy of medications under investigation to treat COVID-19 Abstract Background Treatment of COVID-19 is mostly symptomatic, but a wide range of medications are under investigation against SARS-CoV-2. Although pregnant women are excluded from clinical trials, they will inevitably receive therapies whenever they appear effective in non-pregnant patients and even under compassionate use. Method We conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for COVID-19. Results Regarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, since they are repurposed drugs already used for their established indications. They may thus be used in pregnancy, although their safety in the context of COVID-19 may differ from conventional use. These include the HIV protease inhibitors such as lopinavir/ritonavir which have low placental transfer; interferon which does not cross the placental barrier, and (hydroxy) chloroquine, which have high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir and azithromycin, as well as some monoclonals. However, some drugs are strictly prohibited in pregnancy due to known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab and other IL-6 inhibitors, umifenovir and favipiravir have insufficient data on pregnancy outcomes. Conclusion In life-threatening cases of COVID-19, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. While preclinical and placental transfer studies are required for a number of potential anti-SARS CoV2 drugs, several medications can already be used in pregnant women.

negative: What can psychiatrists learn from SARS and MERS outbreaks?

negative: Long-Term Care Facilities and the Coronavirus Epidemic: Practical Guidelines for a Population at Highest Risk

negative: Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus Coronavirus disease 2019 (COVID‐19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest with flu‐like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID‐19‐infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID‐19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well‐controlled HIV who successfully recovered from a mild, flu‐like illness attributed to SARS‐CoV‐2.

negative: Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial Abstract Objectives To assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. Design Multicenter, open-label, randomized controlled trial. Setting 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants 150 patients hospitalized with COVID-19. 75 patients were assigned to HCQ plus SOC and 75 were assigned to SOC alone (control group). Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measures The primary endpoint was the 28-day negative conversion rate of SARS-CoV-2. The assessed secondary endpoints were negative conversion rate at day 4, 7, 10, 14 or 21, the improvement rate of clinical symptoms within 28-day, normalization of C-reactive protein and blood lymphocyte count within 28-day. Primary and secondary analysis was by intention to treat. Adverse events were assessed in the safety population. Results The overall 28-day negative conversion rate was not different between SOC plus HCQ and SOC group (Kaplan-Meier estimates 85.4% versus 81.3%, P=0.341). Negative conversion rate at day 4, 7, 10, 14 or 21 was also similar between the two groups. No different 28-day symptoms alleviation rate was observed between the two groups. A significant efficacy of HCQ on alleviating symptoms was observed when the confounding effects of anti-viral agents were removed in the post-hoc analysis (Hazard ratio, 8.83, 95%CI, 1.09 to 71.3). This was further supported by a significantly greater reduction of CRP (6.986 in SOC plus HCQ versus 2.723 in SOC, milligram/liter, P=0.045) conferred by the addition of HCQ, which also led to more rapid recovery of lymphopenia, albeit no statistical significance. Adverse events were found in 8.8% of SOC and 30% of HCQ recipients with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea (10%). Conclusions The administration of HCQ did not result in a higher negative conversion rate but more alleviation of clinical symptoms than SOC alone in patients hospitalized with COVID-19 without receiving antiviral treatment, possibly through anti-inflammatory effects. Adverse events were significantly increased in HCQ recipients but no apparently increase of serious adverse events. Trial registration ChiCTR2000029868.

negative: COVID-19 and SARS Coronavirus 2: Antibodies for the Immediate Rescue and Recovery Phase

negative: [Pharmacotherapeutics for the New Coronavirus Pneumonia]. The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.

negative: The long‐term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status Background and objective: Severe acute respiratory syndrome (SARS) emerged in 2003 and its long‐term sequelae remain largely unclear. This study examined the long‐term outcome of pulmonary function, exercise capacity, health and work status among SARS survivors. Methods: A prospective cohort study of SARS patients at the Prince of Wales Hospital, Hong Kong was conducted, with serial assessments of lung function, 6MWD and 36 item Short Form General Health Survey at 3, 6, 12, 18 and 24 months after disease onset. The work status was also recorded. Results: Serial assessments were completed by 55 of the 123 (39.9%) subjects, of whom 27 were health‐care workers (HCW). The mean age of the group was 44.4 (SD 13.2) years and 19 (34.5%) were males. At 24 months, 10 (18.2%), 9 (16.4%), 6 (10.9%) and 29 (52.7%) subjects had FEV(1), FVC, TLC and DL(CO) < 80% of predicted values, respectively. The mean (SD) 6MWD increased significantly from 439.0 (89.1) m at 3 months to 460.1 (102.8) m at 6 months (P 0.016) and became steady after 6 months. However, 6MWD and 36 item Short Form General Health Survey scores were lower than the normal population throughout the study. Moreover, 29.6% of HCW and 7.1% of non‐HCW had not returned to work 2 years after illness onset. Conclusions: This 2‐year study of a selected population of SARS survivors, showed significant impairment of DL(CO), exercise capacity and health status persisted, with a more marked adverse impact among HCW.

negative: COVID-19: ICU delirium management during SARS-CoV-2 pandemic The novel coronavirus, SARS-CoV-2-causing Coronavirus Disease 19 (COVID-19), emerged as a public health threat in December 2019 and was declared a pandemic by the World Health Organization in March 2020. Delirium, a dangerous untoward prognostic development, serves as a barometer of systemic injury in critical illness. The early reports of 25% encephalopathy from China are likely a gross underestimation, which we know occurs whenever delirium is not monitored with a valid tool. Indeed, patients with COVID-19 are at accelerated risk for delirium due to at least seven factors including (1) direct central nervous system (CNS) invasion, (2) induction of CNS inflammatory mediators, (3) secondary effect of other organ system failure, (4) effect of sedative strategies, (5) prolonged mechanical ventilation time, (6) immobilization, and (7) other needed but unfortunate environmental factors including social isolation and quarantine without family. Given early insights into the pathobiology of the virus, as well as the emerging interventions utilized to treat the critically ill patients, delirium prevention and management will prove exceedingly challenging, especially in the intensive care unit (ICU). The main focus during the COVID-19 pandemic lies within organizational issues, i.e., lack of ventilators, shortage of personal protection equipment, resource allocation, prioritization of limited mechanical ventilation options, and end-of-life care. However, the standard of care for ICU patients, including delirium management, must remain the highest quality possible with an eye towards long-term survival and minimization of issues related to post-intensive care syndrome (PICS). This article discusses how ICU professionals (e.g., physicians, nurses, physiotherapists, pharmacologists) can use our knowledge and resources to limit the burden of delirium on patients by reducing modifiable risk factors despite the imposed heavy workload and difficult clinical challenges posed by the pandemic.

negative: COVID-19: An Early Review of Its Global Impact and Considerations for Parkinson’s Disease Patient Care While many infectious disorders are unknown to most neurologists, COVID-19 is very different. It has impacted neurologists and other health care workers, not only in our professional lives but also through the fear and panic within our own families, colleagues, patients and their families, and even in the wider public. COVID-19 affects all sorts of individuals, but the elderly with underlying chronic conditions are particularly at risk of severe disease, or even death. Parkinson’s disease (PD) shares a common profile as an age-dependent degenerative disorder, frequently associated with comorbidities, particularly cardiovascular diseases, so PD patients will almost certainly fall into the high-risk group. Therefore, the aim of this review is to explore the risk of COVID-19 in PD based on the susceptibility to severe disease, its impact on PD disease severity, potential long-term sequelae, and difficulties of PD management during this outbreak, where neurologists face various challenges on how we can maintain effective care for PD patients without exposing them, or ourselves, to the risk of infection. It is less than six months since the identification of the original COVID-19 case on New Year’s Eve 2019, so it is still too early to fully understand the natural history of COVID-19 and the evidence on COVID-19-related PD is scant. Though the possibilities presented are speculative, they are theory-based, and supported by prior evidence from other neurotrophic viruses closely related to SARS-CoV-2. Neurologists should be on high alert and vigilant for potential acute and chronic complications when encountering PD patients who are suspected of having COVID-19.

negative: Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from “cytokine storm syndrome”, resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing “cytokine storm syndrome” and respiratory distress in patients with COVID-19 pneumonia.

negative: Pertussis hospitalizations among term and preterm infants: clinical course and vaccine effectiveness BACKGROUND: Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history. METHODS: Medical record data of 0-2y old patients hospitalized for pertussis during 2005–2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington. RESULTS: Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93–96%) and 73% (95% CI 20–91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively). CONCLUSIONS: Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.

negative: Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities Importance: Patients in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to advanced age and multiple comorbidities. Without effective treatments, outbreaks in such facilities will become commonplace and will result in severe morbidity and mortality. The effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high risk COVID-19 patients in long-term care facilities is not yet understood. Objective: The goal of this analysis is to describe outcomes after use of DOXY-HCQ combination in high-risk COVID-19 patients in LTCF. Design: Case-series analysis. Setting: Three (3) LTCFs in New York. Participants: From March 19 to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and diagnosed (confirmed or presumed) with COVID-19, were included in this analysis. Exposure: All patients who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination therapy along with standard of care. Main Outcomes and Measures: Patients characteristics, clinical recovery, radiological improvements, medication side-effects, hospital transfer, and death were assessed as outcome measures. Results: A series of fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as: resolution of fever and SOB, or a return to baseline setting if patients are ventilator-dependent. A total of 11% (n=6) patients were transferred to acute care hospitals due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect Comparison suggests these data were significantly better outcomes than the data reported in MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington where 57% patients were hospitalized, and 22% patients died. Conclusion: The clinical experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is associated with a reduction in clinical recovery, decreased transfer to hospital and decreased mortality were observed after treatment with DOXY-HCQ.

negative: Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

negative: Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study Abstract Background Different degrees of disorders are reported in respiratory function, physical function and psychological function in patients with corona virus disease 2019 (COVID-19), especially in elderly patients. With the experience of improved and discharged COVID-19 patients, timely respiratory rehabilitation intervention may improve prognosis, maximize functional preservation and improve quality of life (QoL), but there lacks of studies worldwide exploring the outcome of this intervention. Objective To investigate the effects of 6-week respiratory rehabilitation training on respiratory function, QoL, mobility and psychological function in elderly patients with COVID-19. Methods This paper reported the findings of an observational, prospective, quasi-experimental study, which totally recruited 72 participants, of which 36 patients underwent respiratory rehabilitation and the rest without any rehabilitation intervention. The following outcomes were measured: pulmonary function tests including plethysmography and diffusing lung capacity for carbon monoxide (DLCO), functional tests (6-min walk distance test), Quality of life (QoL) assessments (SF-36 scores), activities of daily living (Functional Independence Measure, FIM scores), and mental status tests (SAS anxiety and SDS depression scores). Results After 6 weeks of respiratory rehabilitation in the intervention group, there disclosed significant differences in FEV1(L), FVC(L), FEV1/FVC%, DLCO% and 6-min walk test. The SF-36 scores, in 8 dimensions, were statistically significant within the intervention group and between the two groups. SAS and SDS scores in the intervention group decreased after the intervention, but only anxiety had significant statistical significance within and between the two groups. Conclusions Six-week respiratory rehabilitation can improve respiratory function, QoL and anxiety of elderly patients with COVID-19, but it has little significant improvement on depression in the elderly.

negative: An Analytical Perspective on Pandemic Recovery. After implementing restrictions to curb the spread of coronavirus, governments in the United States and around the world are trying to identify the path to social and economic recovery. The White House and the Centers for Disease Control and Prevention have published guidelines to assist US states, counties, and territories in planning these efforts. As the impact of the coronavirus pandemic has not been uniform, these central guidelines need to be translated into practice in ways that recognize variation among jurisdictions. We present a core methodology to assist governments in this task, presenting a case for appropriate actions at each stage of recovery based on scientific data and analysis. Specifically, 3 types of data are needed: data on the spread of disease should be analyzed alongside data on the overall health of the population and data on infrastructure-for example, the capacity of health systems. Local circumstances will produce different needs and present different setbacks, and governments may need to reinstate as well as relax restrictions. Transparent, defensible analysis can assist in making these decisions and communicating them to the public. In the absence of a widely administered vaccine, analysis remains one of our most important tools in addressing the coronavirus pandemic.

negative: Abstracts of the Tenth Conference of the Federation of Infection Societies, 2003

negative: Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study BACKGROUND: The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19). METHODS: Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ(2) test or Fisher exact test as appropriate. RESULTS: Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 [62, 74] vs. 40 [33, 57] years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ(2) = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 [6.5, 12.0] vs. 7.0 [5.0, 10.0] days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ(2) = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ(2) = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 [77, 91]% vs. 97 [95, 98]%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 [4.87, 11.17] vs. 4.52 [3.62, 5.88] ×10(9)/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 [0.40, 0.79] vs. 1.00 [0.72, 1.27] ×10(9)/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 [4.45, 12.73]% vs. 23.50 [15.27, 31.25]%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 [4.45, 12.73]% vs. 2.91 [1.79, 6.13]%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 [15.00, 34.00] vs. 18.70 [13.00, 30.38] U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 [27.00, 47.00] vs. 22.00 [17.65, 31.75] U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 [72.00, 133.50] vs. 65.00 [54.60, 78.75] μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 [35.00, 170.28] vs. 3.22 [1.04, 21.80] mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 [35.00, 170.28] vs. 81.60 [27.23, 179.08] mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ(2) = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ(2) = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ(2) = 23.257, P < 0.001), shock (11.9% vs. 0%, χ(2) = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ(2) = 7.655, P = 0.006). CONCLUSIONS: Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.

negative: Ethical and Philosophical Consideration of the Dual-use Dilemma in the Biological Sciences The dual-use dilemma arises in the context of research in the biological and other sciences as a consequence of the fact that one and the same piece of scientific research sometimes has the potential to be used for bad as well as good purposes. It is an ethical dilemma since it is about promoting good in the context of the potential for also causing harm, e.g., the promotion of health in the context of providing the wherewithal for the killing of innocents. It is an ethical dilemma for the researcher because of the potential actions of others, e.g., malevolent non-researchers who might steal dangerous biological agents, or make use of the original researcher’s work. And it is a dilemma for governments concerned with the security of their citizens, as well as their health. In this article we construct a taxonomy of types of “experiments of concern” in the biological sciences, and thereby map the terrain of ethical risk. We then provide a series of analyses of the ethical problems and considerations at issue in the dual-use dilemma, including the impermissibility of certain kinds of research and possible restrictions on dissemination of research results given the risks to health and security. Finally, we explore the main available institutional responses to some of the specific ethical problems posed by the dual-use dilemma in the biological sciences.

negative: End-of-life care in patients with a highly transmissible respiratory virus: implications for COVID-19 Symptom management and end-of-life care are core skills for all physicians, although in ordinary times many anesthesiologists have fewer occasions to use these skills. The current coronavirus disease (COVID-19) pandemic has caused significant mortality over a short time and has necessitated an increase in provision of both critical care and palliative care. For anesthesiologists deployed to units caring for patients with COVID-19, this narrative review provides guidance on conducting goals of care discussions, withdrawing life-sustaining measures, and managing distressing symptoms.

negative: Strategies for daily operating room management of ambulatory surgery centers following resolution of the acute phase of the COVID-19 pandemic Abstract We performed a narrative review to explore the economics of daily operating room management decisions for ambulatory surgery centers following resolution of the acute phase of the Coronavirus Disease 2019 (COVID-19) pandemic. It is anticipated that there will be a substantive fraction of patients who will be contagious, but asymptomatic at the time of surgery. Use multimodal perioperative infection control practices (e.g., including patient decontamination) and monitor performance (e.g., S. aureus transmission from patient to the environment). The consequence of COVID-19 is that such processes are more important than ever to follow because infection affects not only patients but the surgery center staff and surgeons. Dedicate most operating rooms to procedures that are not airway aerosol producing and can be performed without general anesthesia. Increase throughput by performing nerve blocks before patients enter the operating rooms. Bypass the phase I post-anesthesia care unit whenever possible by appropriate choices of anesthetic approach and drugs. Plan long-duration workdays (e.g., 12-h). For cases where the surgical procedure does not cause aerosol production, but general anesthesia will be used, have initial (phase I) post-anesthesia recovery in the operating room where the surgery was done. Use anesthetic practices that achieve fast initial recovery of the brief ambulatory cases. When the surgical procedure causes aerosol production (e.g., bronchoscopy), conduct phase I recovery in the operating room and use multimodal environmental decontamination after each case. Use statistical methods to plan for the resulting long turnover times. Whenever possible, have the anesthesia and nursing teams stagger cases in more than one room so that they are doing one surgical case while the other room is being cleaned. In conclusion, this review shows that COVID-19 will markedly affect daily ambulatory workflow for patients undergoing general anesthesia, with potentially substantial economic impact for some surgical specialties.

negative: Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals Background The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. Challenges The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. Purpose This statement aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.

negative: COVID-19 Pandemic: Considerations for Safe Medication Use in Older Adults with Multimorbidity and Polypharmacy

negative: Remdesivir investigational trials in COVID-19: a critical reappraisal Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.

negative: Keeping a cut above the coronavirus disease: surgical perspectives from a public health institution in Singapore during Covid-19

negative: Analysis and Prediction of COVID-19 Pandemic in Pakistan using Time-dependent SIR Model The current outbreak is known as Coronavirus Disease or COVID-19 caused by the virus SAR-COV-2 which continues to wreak havoc across the globe. The World Health Organization (WHO) has declared the outbreak a Public Health Emergency of International Concern. In Pakistan, the spread of the virus is on the rise with the number of infected people and causalities rapidly increasing. In the absence of proper vaccination and treatment, to reduce the number of infections and casualties, the only option so far is to educate people regarding preventive measures and to enforce countrywide lock-down. Any strategy about the preventive measures needs to be based upon detailed analysis of the COVID-19 outbreak and accurate scientific predictions. In this paper, we conduct mathematical and numerical analysis to come up with reliable and accurate predictions of the outbreak in Pakistan. The time-dependent Susceptible-Infected-Recovered (SIR) model is used to fit the data and provide future predictions. The turning point of the peak of the pandemic is defined as the day when the transmission rate becomes less than the recovering rate. We have predicted that the outbreak will reach its maximum peak occurring from late May to 9 June with unrecovered number of Infectives in the range 20000-47000 and the cumulative number of infected cases in the range of 57500-153100. The number of Infectives will remain at the lower end in the lock-down scenario but can rapidly double or triple if the spread of the epidemic is not curtailed and localized. The uncertainty on single day projection in our analysis after April 15 is found to be within 5\%.

negative: Prognostication and Proactive Planning in COVID-19 Abstract Accurate prognostication is challenging in the setting of SARS-CoV-2, the virus responsible for COVID-19, due to rapidly changing data, studies that are not generalizable and lack of morbidity and functional outcomes in survivors. To provide meaningful guidance to patients, existing mortality data must be considered and appropriately applied. While most people infected with SARS-CoV-2 will recover, mortality increases with age and co-morbidity in those who develop severe illness.

negative: Deaths from Covid-19: Who are the forgotten victims? Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.

negative: [Sero-epidemiological characteristics of antibody to SARS-associated coronavirus in Gansu Province]. OBJECTIVE To study the levels of SARS-associated coronavirus IgG antibody of SARS patients, people who closely contacted SARS patients and normal subjects in Gansu province. METHODS The levels of SARS-associated coronavirus IgG antibody were measured by ELISA. The material included acute and (or) recovery period sera of 9 SARS patients, sera from 1,109 doctors and nurses closely contacted with SARS patients, laboratory workers, personnel for disease control and prevention, persons who contacted SARS patients, and sera from 978 normal subjects. RESULTS SARS coronavirus IgG antibody was detected positive in 6 of the 9 patients, it was still positive in the sera twelve months after recovery; 1 of the closely contacted persons and 3 normal subjects were found positive. CONCLUSION The positive rate of SARS coronavirus IgG antibody of patients was consistent with the clinical diagnosis. The low positive rate of the persons who closely contacted SARS patients and normal subjects suggests that SARS probably had no subclinical infection.

negative: Abstracts of FIS/HIS 2016 – Poster Presentations

negative: Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

negative: ELM—the database of eukaryotic linear motifs Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances.

negative: On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity- dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase at https://github.com/aangelopoulos/cfr-covid-19 .

negative: Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy.

negative: Effects of Coronavirus Disease 2019 (COVID-19) on Maternal, Perinatal and Neonatal Outcomes: a Systematic Review of 266 Pregnancies Objective: To perform a systematic review of available published literature on pregnancies affected by COVID-19 to evaluate the effects of COVID-19 on maternal, perinatal and neonatal outcomes. Methods: We performed a systematic review to evaluate the effects of COVID-19 on pregnancy, perinatal and neonatal outcomes. We conducted a comprehensive literature search using PubMed, EMBASE, Cochrane library, China National Knowledge Infrastructure Database and Wan Fang Data until April 20, 2020 (studies were identified through PubMed alert after April 20, 2020). For the research strategy, combinations of the following keywords and MeSH terms were used: SARS-CoV-2, COVID-19, coronavirus disease 2019, pregnancy, gestation, maternal, mothers, vertical transmission, maternal-fetal transmission, intrauterine transmission, neonates, infant, delivery. Eligibility criteria included laboratory-confirmed and/or clinically diagnosed COVID-19, patient was pregnant on admission, availability of clinical characteristics, including maternal, perinatal or neonatal outcomes. Exclusion criteria were unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, and unreported maternal or perinatal outcomes. No language restrictions were applied. Results: We identified several case-reports and case-series but only 19 studies, including a total of 266 pregnant women with COVID-19, met eligibility criteria and were finally included in the review. In the combined data from seven case-series, the maternal age ranged from 20 to 41 years and the gestational age on admission ranged from 5 to 41 weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath and fatigue. The rate of severe pneumonia was relatively low, with the majority of the cases requiring intensive care unit admission. Almost all cases from the case-series had positive computer tomography chest findings. There were six and 22 cases that had nucleic-acid testing in vaginal mucus and breast milk samples, respectively, which were negative for SARS-CoV-2. Only a few cases had spontaneous miscarriage or abortion. 177 cases had delivered, of which the majority by Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at 1 and 5 minutes ranged from 7 to 10 and 8 to 10, respectively. A few neonates had birthweight less than 2500 grams and over one-third of cases were transferred to neonatal intensive care unit. There was one case each of neonatal asphyxia and neonatal death. There were 113 neonates that had nucleic-acid testing in throat swab, which was negative for SARS-CoV-2. From the case-reports, two maternal deaths among pregnant women with COVID-19 were reported. Conclusions: The clinical characteristics of pregnant women with COVID-19 are similar to those of nonpregnant adults with COVID-19. Currently, there is no evidence that pregnant women with COVID-19 are more prone to develop severe pneumonia, in comparison to nonpregnant patients. The subject of vertical transmission of SARS-CoV-2 remains controversial and more data is needed to investigate this possibility. Most importantly, in order to collect meaningful pregnancy and perinatal outcome data, we urge researchers and investigators to reference previously published cases in their publications and to record such reporting when the data of a case is being entered into a registry or several registries.

negative: TAVR during the COVID19 Pandemic: The ACC/SCAI Consensus Statement

negative: Endocrine and metabolic link to coronavirus infection Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19.

negative: Prediction for the spread of COVID-19 in India and effectiveness of preventive measures Abstract The spread of COVID-19 in the whole world has put the humanity at risk. The resources of some of the largest economies are stressed out due to the large infectivity and transmissibility of this disease. Due to the growing magnitude of number of cases and its subsequent stress on the administration and health professionals, some prediction methods would be required to predict the number of cases in future. In this paper, we have used data-driven estimation methods like long short-term memory (LSTM) and curve fitting for prediction of the number of COVID-19 cases in India 30 days ahead and effect of preventive measures like social isolation and lockdown on the spread of COVID-19. The prediction of various parameters (number of positive cases, number of recovered cases, etc.) obtained by the proposed method is accurate within a certain range and will be a beneficial tool for administrators and health officials.

negative: Certain Emerade adrenaline auto-injector pens being recalled in UK

negative: Recurrence of positive SARS‐CoV‐2 in patients recovered from COVID‐19 Recurrence of positive SARS CoV‐2 PCR has been described in patients discharged from hospital after 2 consecutive negative PCR. We discuss possible explanations including false negative, reactivation and re‐infection and propose different strategy to solve this issue. Prolonged SARS‐CoV‐2 RNA shedding and recurrence of viral RNA shedding in asymptomatic patients remain unknown. Transmission of SARS‐CoV‐2 by asymptomatic carriers had been documented. Considering the significance of this ongoing global public health emergency, it is necessary to carry out large studies to better understand the issue of potential SARS‐CoV‐2 recurrence in COVID‐19 patients. This article is protected by copyright. All rights reserved.

negative: Influenza D Virus in Cattle, France, 2011–2014 A new influenza virus, genus D, isolated in US pigs and cattle, has also been circulating in cattle in France. It was first identified there in 2011, and an increase was detected in 2014. The virus genome in France is 94%–99% identical to its US counterpart, which suggests intercontinental spillover.

negative: Neurological Manifestations of COVID‐19: A systematic review and current update The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was first identified in December of 2019 in the city of Wuhan, China. Since the outbreak, various reports detail its symptoms and outcomes, primarily focusing on respiratory complications. However, reports are emerging of the virus’ effects systemically, including that of the nervous system. A review of all current published literature was conducted, and we report that headache and anosmia were common neurological manifestations of SARS‐CoV‐2. Less common symptoms include seizure, stroke and isolated cases of Guillain‐Barre syndrome. Further research is now warranted to precisely determine the relationship between those patients developing neurological sequelae, their clinical state and any subsequent morbidity and mortality.

negative: Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection OBJECTIVE: To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS: Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS: Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION: One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.

negative: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses. The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19 The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene which is involved in regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs which negatively correlated with the expression of genes that code for sterol response element binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Together our results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

negative: Optimistic bias, information seeking and intention to undergo prostate cancer screening: A Taiwan study on male adults Abstract Background This study explores optimistic bias and information seeking in prostate cancer patients and how they impact intention to undergo prostate cancer screening. Methods A national sample of 427 Taiwanese male adults aged at least 45 years (mean (M)=57) were recruited to complete a telephone-based survey questionnaire between April 30 and May 8, 2008. Results The questionnaire results showed that respondents considered themselves less likely than others to get prostate cancer. The relationship between optimistic bias and intention to undergo prostate cancer screening was non-significant, while information seeking positively and significantly predicted such an intention. Conclusions The findings of this study imply that health educators should include risk-awareness strategies and information seeking interventions in the design of cancer prevention programs.

negative: The role of cardiac imaging in hospitalized COVID-19-positive patients. COVID-19 infection is associated with several cardiac complications with high rates of adverse outcomes. Cardiac imaging has different utility in different clinical scenarios, and the importance of minimizing healthcare worker exposure should be considered. Cardiac imaging should only be ordered if its benefits outweigh its risks, with anticipated changes in acute treatment and outcomes, and no suitable alternative of sufficient adequacy is available. Indications for advanced cardiac imaging for COVID-19 patients in the acute phase are limited, although follow-up imaging in the convalescent stage may provide prognostic importance in recovered COVID-19 patients with positive troponin or decompensated heart failure.

negative: The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

negative: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.

negative: Editorial: EAERE, ERE and the Research Challenges of the Coronavirus Pandemic

negative: Efficient network immunization under limited knowledge Targeted immunization or attacks of large-scale networks has attracted significant attention by the scientific community. However, in real-world scenarios, knowledge and observations of the network may be limited thereby precluding a full assessment of the optimal nodes to immunize (or remove) in order to avoid epidemic spreading such as that of current COVID-19 epidemic. Here, we study a novel immunization strategy where only n nodes are observed at a time and the most central between these n nodes is immunized (or attacked). This process is continued repeatedly until 1-p fraction of nodes are immunized (or attacked). We develop an analytical framework for this approach and determine the critical percolation threshold pc and the size of the giant component P∞ for networks with arbitrary degree distributions P(k). In the limit of n→∞ we recover prior work on targeted attack, whereas for n=1 we recover the known case of random failure. Between these two extremes, we observe that as n increases, pc increases quickly towards its optimal value under targeted immunization (attack) with complete information. In particular, we find a new scaling relationship between |pc(∞) -pc (n)| and n as |pc(∞) -pc (n)|~n-1exp(-α n). For Scale-free (SF) networks, where P(k)~k-γ,2<γ<3), we find that pc has a transition from zero to non-zero when n increases from n=1 to order of logN (N is the size of network). Thus, for SF networks, knowledge of order of logN nodes and immunizing them can reduce dramatically an epidemics.

negative: Temperature significant change COVID-19 Transmission in 429 cities Background There is no evidence supporting that temperature changes COVID-19 transmission. Methods We collected the cumulative number of confirmed cases of all cities and regions affected by COVID-19 in the world from January 20 to February 4, 2020, and calculated the daily means of the average, minimum and maximum temperatures in January. Then, restricted cubic spline function and generalized linear mixture model were used to analyze the relationships. Results There were in total 24,232 confirmed cases in China and 26 overseas countries. In total, 16,480 cases (68.01%) were from Hubei Province. The lgN rose as the average temperature went up to a peak of 8.72℃ and then slowly declined. The apexes of the minimum temperature and the maximum temperature were 6.70℃ and 12.42℃ respectively. The curves shared similar shapes. Under the circumstance of lower temperature, every 1℃ increase in average, minimum and maximum temperatures led to an increase of the cumulative number of cases by 0.83, 0.82 and 0.83 respectively. In the single-factor model of the higher-temperature group, every 1℃ increase in the minimum temperature led to a decrease of the cumulative number of cases by 0.86. Conclusion The study found that, to certain extent, temperature could significant change COVID-19 transmission, and there might be a best temperature for the viral transmission, which may partly explain why it first broke out in Wuhan. It is suggested that countries and regions with a lower temperature in the world adopt the strictest control measures to prevent future reversal.

negative: Three months of informational trends in COVID-19 across New York City In the midst of widespread community transmission of coronavirus disease 2019 (COVID-19) in New York, residents have sought information about COVID-19. We analyzed trends in New York State (NYS) and New York City (NYC) data to quantify the extent of COVID-19-related queries. Data on the number of 311 calls in NYC, Google Trend data on the search term ‘Coronavirus’ and information about trends in COVID-19 cases in NYS and the USA were compiled from multiple sources. There were 1228 994 total calls to 311 between 22 January 2020 and 22 April 2020, with 50 845 calls specific to COVID-19 in the study period. The proportion of 311 calls related to COVID-19 increased over time, while the ‘interest over time’ of the search term ‘Coronavirus’ has exponentially increased since the end of February 2020. It is vital that public health officials provide clear and up-to-date information about protective measures and crucial communications to respond to information-seeking behavior across NYC.

negative: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users.

negative: A systematic review on use of aminoquinolines for the therapeutic management of COVID-19: Efficacy, safety and clinical trials Recent global outbreak of the pandemic caused by coronavirus (COVID-19) emphasizes the urgent need for novel antiviral therapeutics. It can be supplemented by utilization of efficient and validated drug discovery approaches such as drug repurposing/repositioning. The well reported and clinically used anti-malarial aminoquinoline drugs (chloroquine and hydroxychloroquine) have shown potential to be repurposed to control the present pandemic by inhibition of COVID-19. The review elaborates the mechanism of action, safety (side effects, adverse effects, toxicity) and worldwide clinical trials for chloroquine and hydroxychloroquine to benefit the clinicians, medicinal chemist, pharmacologist actively involved in the management of COVID-19 infection.

negative: Effect of preventive actions and health care factors in controlling the outbreaks of COVID-19 pandemic With the insurgence of the COVID-19 pandemic, a large number of people died in the past several months, and the situation is ongoing with increasing panic and vulnerability. Due to the lack of drugs and prophylaxis against COVID-19, most of the countries are now relying on preventive measures focusing on maintaining social distance. However, this social distancing can create global socio-economic threats and psychological disorders. Therefore, these control measures need to have an assessment to evaluate their potential in containing the situation. In this study, we analyzed the outcome of COVID-19 in response to control measures, health care facilities, and prevalent diseases. Based on our findings, the number of COVID-19 deaths found to reduce with increased medical personnel and hospital beds. We found 0.23, 0.16, and 0.21 as the measurement of non-linear relationship between COVID-19 case fatality and number of physicians, nurses and midwives, and hospital beds and these relationships are highly significant with p-value of 0.000007, 0.0046, and 0.0196, respectively. Importantly, we observed a significant correlation between the reduction of COVID-19 cases and the earliness of preventive initiation. As a result, enhancing health care facilities as well as imposing those control measures in a short time could be valuable to prevent the currently raging COVID-19 pandemic. The apathy of taking immediate health care action from the nations has identified as one of the critical reasons to make the circumstances worst. Gambia, Nicaragua, Burundi, Namibia, and Nepal have marked in a state of danger based on the comparative study towards the health care action for the top twenty burdening and least affected countries. Interestingly, no association in most diseases except for few cases has found between the comorbidities and severity of COVID-19, which warranted further investigation at the pathobiological level. We believe that this study could provide a guide for future COVID-19 research.

negative: Risk Factors for Repeat Adverse Asthma Events in Children After Visiting an Emergency Department Objective The aim of this study was to identify risk factors for long-term adverse outcomes in children with asthma after visiting the emergency department (ED). Methods A prospective observational study was conducted at the ED of a pediatric tertiary hospital in Ontario, Canada. Patient outcomes (ie, acute asthma episodes and ED visits) were measured at baseline and at 1- and 6-months post-ED discharge. Time trends in outcomes were assessed using the generalized estimating equations method. Multiple conditional logistic regressions were used to model outcomes at 6 months and examine the impact of drug insurance coverage while adjusting for confounders. Results Of the 269 children recruited, 81.8% completed both follow-ups. ED use significantly reduced from 39.4% at baseline to 26.8% at 6 months (P < .001), whereas the level of acute asthma episodes remained unchanged. Children with drug insurance coverage were less likely to have acute asthma episodes (adjusted odds ratio [AOR] = 0.36; 95% CI, 0.15–0.85; P < .02) or repeat ED visits (AOR = 0.45; 95% CI, 0.20–0.99; P < .05) at 6 months. Other risk factors for adverse outcomes included previous adverse asthma events and certain asthma triggers (eg, cold/sinus infection). Washing bed linens in hot water weekly was protective against subsequent acute asthma episodes. Conclusions Our study demonstrated significant improvements in long-term outcomes in children seeking acute care for asthma in the ED. Future efforts remain in targeting the sustainability of improved outcomes beyond 6 months. Risk factors identified can help target vulnerable populations for proper interventions, which may include efforts to maximize insurance coverage for asthma medications and strategies to improve asthma self-management through patient and provider education.

negative: Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China Summary Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Findings The mean age of the dead was 71.48 years, the average course of the disease was 10.56 days, all patients eventually died of respiratory failure. All of those who died had underlying diseases, the most common of which was hypertension (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases (8/25, 32%), kidney diseases (5/25, 20%), cerebral infarction (4/25, 16%), chronic obstructive pulmonary disease (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death, white blood cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22 patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%). Interpretation The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts.

negative: Use of drugs with potential cardiac effect in the setting of SARS-CoV-2 infection

negative: A Roadmap to Reopening a Neurosurgical Practice in the Age of COVID-19 BACKGROUND: The Coronavirus disease 2019 (COVID-19) outbreak has left a lasting mark on medicine globally. METHODS: Here we outline the steps that the Lenox Hill Hospital/Northwell Health Neurosurgery Department-located within the epicenter of the pandemic in New York City-is currently taking to recover our neurosurgical efforts in the age of COVID-19. RESULTS: We outline measurable milestones to identify the transition to the recovery period and hope these recommendations may serve as a framework for an effective path forward. CONCLUSIONS: We believe that recovery following the COVID-19 pandemic offers unique opportunities to disrupt and rebuild the historical patient and office experience as we evolve with modern medicine in a post-COVID-19 world.

negative: COVID-19 and maternal mental health: Are we getting the balance right? This paper presents a rapid evidence review into the clinical and psychological impacts of COVID-19 on perinatal women and their infants. Literature search revealed that there is very little formal evidence on the impact of COVID-19 on pregnant, labouring and postnatal women or their babies. The clinical evidence to date suggests that pregnant and childbearing women, and their babies are not at increased risk of either getting infected, or of having severe symptoms or consequences than the population as a whole. There is no evidence on the short- and longer-term psychological impacts of restrictive practices or social and personal constraints for childbearing women during COVID-19 in particular, or infection pandemics in general. The potential for adverse mental health consequences of the pandemic should be recognised as a critical public health concern, together with appropriate care and support to prevent and ameliorate any negative impacts.

negative: Disparities in Vulnerability to Severe Complications from COVID-19 in the United States This paper provides the first nationally representative estimates of vulnerability to severe complications from COVID-19 overall and across race-ethnicity and socioeconomic status. We use the Panel Study of Income Dynamics (PSID) to examine the prevalence of specific health conditions associated with complications from COVID-19 and to calculate, for each individual, an index of the risk of severe complications from respiratory infections developed by DeCaprio et al. (2020). We show large disparities across race-ethnicity and socioeconomic status in the prevalence of conditions, including hypertension, which are associated with the risk of severe complications from COVID-19. Moreover, we show that these disparities emerge early in life, prior to age 65, leading to higher vulnerability to such complications. Our results suggest particular attention should be paid to the risk of adverse outcomes in midlife for non-Hispanic blacks, adults with a high school degree or less, and low-income Americans.

negative: Data-based analysis, modelling and forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infectious-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R0), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R0 as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be â¼4.6, while the one computed under the second scenario was found to be â¼3.2. Thus, based on the SIRD simulations, the estimated average value of R0 was found to be â¼2.6 based on confirmed cases and â¼2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with a lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around â¼0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

negative: Investigating the likely association between genetic ancestry and COVID-19 manifestation The novel coronavirus 2019-nCoV/SARS-CoV-2 infection has shown discernible variability across the globe. While in some countries people are recovering relatively quicker, in others, recovery times have been comparatively longer and numbers of those succumbing to it high. In this study, we aimed to evaluate the likely association between an individual's ancestry and the extent of COVID-19 manifestation employing Europeans as the case study. We employed 10,215 ancient and modern genomes across the globe assessing 597,573 single nucleotide polymorphisms (SNPs). Pearson's correlation coefficient (r) between various ancestry proportions of European genomes and COVID-19 death/recovery ratio was calculated and its significance was statistically evaluated. We found significant positive correlation (p=0.03) between European Mesolithic hunter gatherers (WHG) ancestral fractions and COVID-19 death/recovery ratio and a marginally significant negative correlation (p=0.06) between Neolithic Iranian ancestry fractions and COVID-19 death/recovery ratio. We further identified 404 immune response related single nucleotide polymorphisms (SNPs) by comparing publicly available 753 genomes from various European countries against 838 genomes from various Eastern Asian countries in a genome wide association study (GWAS). Prominently we identified that SNPs associated with Interferon stimulated antiviral response, Interferon-stimulated gene 15 mediated antiviral mechanism and 2'-5' oligoadenylate synthase mediated antiviral response show large differences in allele frequencies between Europeans and East Asians. Overall, to the best of our knowledge, this is the first study evaluating the likely association between genetic ancestry and COVID-19 manifestation. While our current findings improve our overall understanding of the COVID-19, we note that the development of effective therapeutics will benefit immensely from a more detailed analyses of individual genomic sequence data from COVID-19 patients of varied ancestries.

negative: Combating devastating COVID-19 by drug repurposing Despite advances in drug discovery, viral infections remain a major challenge for scientists across the globe. The recent pandemic of COVID-19 (coronavirus disease 2019), caused by a viral infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has created a disastrous situation all over the world. As no drugs are available to treat this life-threatening disease and the mortality rate due to COVID-19 is high, there is an utmost need to attempt to treat the infection using drug repurposing. Some countries are against the use of these drugs because of adverse effects associated with drug repurposing and lack of statistically significant clinical data, but they have been found to be effective in some countries to treat COVID-19 patients (off-label/investigational). This article emphasises possible drug candidates in the treatment of COVID-19. Most of these drugs were found to be effective in in vitro studies. There is a need to re-assess in vitro data and to carry out randomised clinical trials. Further investigations of these drugs are recommended on a priority basis.

negative: LB-S&T-36 RECOVERY FROM NEUROLOGIC IMPAIRMENT IN MURINE MODEL OF CORONAVIRUS-INDUCED DEMYELINATION DOES NOT DIRECTLY CORRELATE WITH IMPROVEMENT OF NEUROGENIC BLADDER DYSFUNCTION: LONG-TERM FOLLOW UP STUDY

negative: Analysis of TCM in prevention and treatment of post-traumatic stress disorder induced by COVID-19/ 中医药防治新型冠状病毒肺炎所致创伤后应激障碍用药探析 Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei Province in December 2019, with severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 are all infectious diseases caused by coronavirus. According to the knowledge of infectious diseases such as SARS and MERS, many patients and health care workers suffered from depression and anxiety during and after the epidemic. In particular, post-epidemic survivors were more likely to suffer from post-traumatic stress disorder (PTSD). Similar conditions could be occurred during and after COVID-19. Therefore, it is also an important task to reduce the prevalence of PTSD after COVID-19 as much as possible and to relieve the tension of infected patients, first-line medical staff, quarantine personnel and so on. Traditional Chinese medicine has unique advantages in the treatment of emotional diseases. Understanding the etiology and pathogenesis of PTSD by theory of traditional Chinese medicine and looking for effective methods to treat PTSD will be helpful to treat PTSD of survivors after COVID-19. It is found that Sini Powder has potential value in the treatment of PTSD by the summary and comparison of the research on traditional Chinese medicine related to the treatment of PTSD. We hope to overcome this epidemic psychologically and spiritually. Therefore, it is considered that Sini Powder can be used as the first choice for relieving emotional diseases of related patients during COVID-19 and treating PTSD of survivors after COVID-19.

negative: Analysis on Novel Coronavirus (COVID-19) Using Machine Learning Methods In this paper, we are working on a pandemic of novel coronavirus (COVID-19). COVID-19 is an infectious disease, it creates severe damage in the lungs. COVID-19 causes illness in humans and has killed many people in the entire world. However, this virus is reported as a pandemic by the World Health Organization (WHO) and all countries are trying to control and lockdown all places. The main objective of this work is to solve the five different tasks such as I) Predicting the spread of coronavirus across regions. II) Analyzing the growth rates and the types of mitigation across countries. III) Predicting how the epidemic will end. IV) Analyzing the transmission rate of the virus. V) Correlating the coronavirus and weather conditions. The advantage of doing these tasks to minimize the virus spread by various mitigation, how well the mitigations are working, how many cases have been prevented by this mitigations, an idea about the number of patients that will recover from the infection with old medication, understand how much time will it take to for this pandemic to end, we will be able to understand and analyze how fast or slow the virus is spreading among regions and the infected patient to reduce the spread based clear understanding of the correlation between the spread and weather conditions. In this paper, we propose a novel Support Vector Regression method to analysis five different tasks related to novel coronavirus. In this work, instead of simple regression line we use the supported vectors also to get better classification accuracy. Our approach is evaluated and compared with other well-known regression models on standard available datasets. The promising results demonstrate its superiority in both efficiency and accuracy.

negative: Coronavirus disease 2019: What we know? In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID‐19) by the World Health Organization, respectively. The COVID‐19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID‐19, but also to comment briefly on the epidemiology and pathology based on the current evidence.

negative: The novel coronavirus outbreak: what can be learned from China in public reporting? The new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.

negative: Testing lags and emerging COVID-19 outbreaks in federal penitentiaries in Canada Objectives: To provide the first known comprehensive analysis of COVID-19 outcomes in a federal penitentiary system. We examined the following COVID-19 outcomes within federal penitentiaries and contrasted them with the overall population in the penitentiaries' respective provincial jurisdictions: testing, prevalence, the proportion recovered, and fatality. Methods: Data for prisons were obtained from the Correctional Service of Canada and, for the general population, from COVID-19 Esri Canadian Outbreak Tracking Hub. Data were retrieved between March 30 and April 21, 2020, and are accurate to this date. Penitentiary-, province- and sex-specific frequency statistics for each outcome were calculated. Results: Data on 50 of 51 penitentiaries (98%) were available. Of these, 72% of penitentiaries reported fewer tests per 1000 population than the Canadian general population average (16 tests/1000 population), and 24% of penitentiaries reported zero tests. Penitentiaries with high levels of testing were those that already had elevated COVID-19 prevalence. Five penitentiaries reported an outbreak (at least one case). Hardest hit penitentiaries were those in Quebec and British Columbia, with some prisons reporting COVID-19 prevalence of 30% to 40%. Of these, two were women's prisons. Female prisoners were over-represented among cases (31% of cases overall, despite representing 5% of the total prison population). Conclusion: Increased sentinel or universal testing may be appropriate given the confined nature of prison populations. This, along with rigorous infection prevention control practices and the potential release of prisoners, will be needed to curb current outbreaks and those likely to come.

negative: Cardiac involvement in COVID‐19 patients: Risk factors, predictors, and complications: A review BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS‐CoV‐2/COVID‐19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID‐19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID‐19. RESULTS: Notably, COVID‐19 patients with pre‐existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID‐19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID‐19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID‐19 patients to promote more informed treatment and, ultimately, better clinical outcomes.

negative: Estimating required lockdown cycles before immunity to SARS-CoV-2: Model-based analyses of susceptible population sizes, S0, in seven European countries including the UK and Ireland Background: Following stringent social distancing measures, some European countries are beginning to report a slowed or negative rate of growth of daily case numbers testing positive for the novel coronavirus. The notion that the first wave of infection is close to its peak begs the question of whether future peaks or second waves are likely. We sought to determine the current size of the effective (i.e. susceptible) population for seven European countries - to estimate immunity levels following this first wave. We compare these numbers to the total population sizes of these countries, in order to investigate the potential for future peaks. Methods: We used Bayesian model inversion to estimate epidemic parameters from the reported case and death rates from seven countries using data from late January 2020 to April 5th 2020. Two distinct generative model types were employed: first a continuous time dynamical-systems implementation of a Susceptible-Exposed-Infectious-Recovered (SEIR) model and second: a partially observable Markov Decision Process (MDP) or hidden Markov model (HMM) implementation of an SEIR model. Both models parameterise the size of the initial susceptible population (S0), as well as epidemic parameters. Parameter estimation (data fitting) was performed using a standard Bayesian scheme (variational Laplace) designed to allow for latent unobservable states and uncertainty in model parameters. Results: Both models recapitulated the dynamics of transmissions and disease as given by case and death rates. The peaks of the current waves were predicted to be in the past for four countries (Italy, Spain, Germany and Switzerland) and to emerge in 0.5-2 weeks in Ireland and 1-3 weeks in the UK. For France one model estimated the peak within the past week and the other in the future in two weeks. Crucially, Maximum a posteriori (MAP) estimates of S0 for each country indicated effective population sizes of below 20% (of total population size), under both the continuous time and HMM models. Using for all countries, with a Bayesian weighted average across all seven countries and both models, we estimated that 6.4% of the total population would be immune. From the two models the maximum percentage of the effective population was estimated at 19.6% of the total population for the UK, 16.7% for Ireland, 11.4% for Italy, 12.8% for Spain, 18.8% for France, 4.7% for Germany and 12.9% for Switzerland. Conclusion: Our results indicate that after the current wave, a large proportion of the total population will remain without immunity. This suggests that in the absence of strong seasonal effects, new medications or more comprehensive contact tracing, a further set of epidemic waves in different geographic centres are likely. These findings may have implications for exit strategies from any lockdown stage.

negative: Reply to Kesici et al. and Zeng et al.: Blocking the virus and reducing the inflammatory damage in COVID-19

negative: A global treatments for coronaviruses including COVID‐19 In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019‐nCoV). So far, there are no specific treatments for patients with coronavirus disease‐19 (COVID‐19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome‐related coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID‐19. Cathepsin L is required for entry of the 2019‐nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin‐converting‐enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID‐19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019‐nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS‐CoV disease and can be useful for patients of COVID‐19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS‐CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS‐CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID‐19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.

negative: Blood glucose is a representative of the clustered indicators of multi-organ injury for predicting mortality of COVID-19 in Wuhan, China OBJECTIVE Most patients with Coronavirus Disease 2019 (COVID-19) were Mild or Moderate. Severe patients progressed rapidly to Critical condition including multi-organ failure and even death. Identification of early predictive factors is urgently necessary to facilitate appropriate intensive care. METHODS We included all patient admitted to Wuhan Union Hospital and treated by the supportive medical team of Beijing Tongren Hospital as of March 20, 2020. Indicators of injuries for multiple organs, including the heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting primary outcomes (an intensive care unit (ICU) or death). RESULTS The data of 120 patients with a severity equal to or greater than Moderate, discharged or died were extracted. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. There were 26 cases with primary outcomes including 16 deaths. Univariable analysis indicated that fasting blood glucose (FBG), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase and creatinine were associated with primary outcomes and death. Among patients with primary outcomes, although FBG levels were much higher on admission, they dramatically decreased subsequently, while in deceased patients they increased continuously. Multivariable Cox regression indicated that FBG≥7mmol/L was the only independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Cluster analysis found more proximities of FBG (at the time of admission) with LDH, HDDH or Creatinine (after 2-4 days of hospitalization) (r=0.43, 0.43 and 0.50, respectively, P<0.01 for all). Conclusions Blood glucose is a representative of the clustered indicators of multi-organ injury and earlier predictor for poor outcomes and death in the COVID patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be much helpful for predicting poor outcomes to facilitate appropriate intensive care.

negative: Diabetes and metabolic syndrome as risk factors for COVID-19 BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.

negative: PCR Assays Turned Positive in 25 Discharged COVID-19 Patients We report the observation that 14.5% of COVID-19 patients had positive RT-PCR testing again after discharge. We describe correlations between laboratory parameters and treatment duration (r= -0.637; p=0.002) and time to virus recrudescence (r= 0.52; p=0.008) respectively, suggesting the need for additional measures to confirm illness resolution in COVID-19 patients.

negative: Public policy and economic dynamics of COVID-19 spread: a mathematical modeling study Summary Background: With the COVID-19 pandemic infecting millions of people, largescale quarantine policies have been enacted across the globe. Understanding how to maximize the effectiveness of these policies while mitigating economic damage is essential. We develop a mathematical model with different levels of population health and economic risk to assess the impact of quarantine measures on deaths, hospitalizations, and economic output. Methods: We combine an extended SEIR model that has multiple levels of health risk and economic vulnerability with disease parameters for the COVID19 pandemic to study the effects of quarantine policies. We examine the dynamics of infectious disease transmission and its economic impact for one year. We populate our model with a baseline of 95.6 % of high-risk people and 85.6 % of low-risk people in quarantine. We use our model to simulate leaving the current quarantine restrictions in place indefinitely. We then assess a policy where quarantine restrictions for lower-risk groups are gradually relaxed. Finally, we simulate relaxing quarantine restrictions more quickly. To compare outbreak outcomes under the same quarantine policies using different disease parameters, we also perform a sensitivity analysis on the contagiousness of infected people, the strictness of social isolation measures, and the amount that public policymakers value the economy in setting quarantine restrictions. Findings: We first consider a baseline scenario with constant quarantine level, finding that in a population of 330,000,000 million, there are 32,023 deaths among those under 60 and 174,682 deaths among those over 60, there is a peak of 189,136 hospitalizations, and the economy relative to the beginning of the quarantine state is 1.4 % smaller. In the scenario where higher-risk people are strictly quarantined, and for others the quarantine is slowly relaxed, there are 63,776 deaths among those under 60, 85,880 deaths among those over 60, a peak of 341,321 hospitalizations, and the economy relative to the beginning of the quarantine state is 6% larger. In the scenario where quarantine is more quickly lifted, there are 25,720 deaths among those under 60, 214,718 deaths among those over 60, a peak of 341,321 hospitalizations, and economic output relative to the beginning of the quarantine state is 4.5 % smaller. Interpretation: Strict restrictions on high-risk patients and a gradual lifting of quarantine for low-risk patients results in a limited number of deaths and lesser economic damage. We recommend this kind of strategy, combined with policies lowering the contagiousness of the disease and making quarantine more tolerable and economically viable for individuals.

negative: COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach Abstract Background The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. Methods In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. Results After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. Discussion This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.

negative: Outbreak dynamics of COVID-19 in China and the United States On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n=30 provinces, we found a latent period of 2.56+/-0.72 days, a contact period of 1.47+/-0.32 days, and an infectious period of 17.82+/-2.95 days. We assume that the latent and infectious periods are disease-specific and the contact period is behavior-specific and can vary between different communities, states, or countries. For the early stages of the outbreak in the United States, in n=50 states, we adopted the latent and infectious periods from China, and found a contact period of 3.38+/-0.69 days. Our network model predicts that - without the massive political mitigation strategies that are in place today - the United states would have faced a basic reproduction number of 5.3+/-0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lock down, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.

negative: Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. A previously undescribed coronavirus (CoV) is the etiologic agent responsible for severe acute respiratory syndrome (SARS). Using a panel of contiguous cDNAs that span the entire genome, we have assembled a full-length cDNA of the SARS-CoV Urbani strain, and have rescued molecularly cloned SARS viruses (infectious clone SARS-CoV) that contained the expected marker mutations inserted into the component clones. Recombinant viruses replicated as efficiently as WT virus and both were inhibited by treatment with the cysteine proteinase inhibitor (2S,3S)-transepoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester. In addition, subgenomic transcripts were initiated from the consensus sequence ACGAAC in both the WT and infectious clone SARS-CoV. Availability of a SARS-CoV full-length cDNA provides a template for manipulation of the viral genome, allowing for the rapid and rational development and testing of candidate vaccines and therapeutics against this important human pathogen.

negative: Association between Clinical, Laboratory and CT Characteristics and RT-PCR Results in the Follow-up of COVID-19 patients Abstract Background: Since December 2019, more than 100,000 coronavirus disease 2019 (COVID-19) patients have been confirmed globally based on positive viral nucleic acids with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). However, the association between clinical, laboratory and CT characteristics and RT-PCR results is still unclear. We sought to examine this association in detail, especially in recovered patients. Methods: We analysed data from 52 confirmed patients who had been discharged with COVID-19. The clinical, laboratory, and radiological data were dynamically recorded and compared with the admission and follow-up RT-PCR results. Results: In this cohort, 52 admitted COVID-19 patients who had confirmed positive RT-PCR results were discharged after 2 rounds of consecutively negative RT-PCR results. Compared with admission levels, CRP levels (median 4.93 mg/L [IQR: 1.78-10.20]) decreased significantly (p<0.001). and lymphocyte counts (median 1.50×109/L [IQR: 1.11-1.88]) increased obviously after obtaining negative RT-PCR results (p<0.001). Additionally, substantially improved inflammatory exudation was observed on chest CT except for 2 progressed patients. At the two-week follow-up after discharge, 7 patients had re-positive RT-PCR results, including the abovementioned 2 progressed patients. Among the 7 patients, new GGO was demonstrated in 2 patients. There were no significant differences in CPR levels or lymphocyte counts when comparing the negative and re-positive PCT results (all p >0.05). Conclusion: Heterogeneity between CT features and RT-PCR results was found in COVID-19, especially in some recovered patients with negative RT-PCR results. Our study highlights that both RT-PCR and chest CT should be considered as the key determinants for the diagnosis and management of COVID-19 patients.

negative: COVID-19 and pregnancy: a review of current knowledge. BACKGROUND Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.

negative: Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis Abstract Background Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. Methods Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. Results The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3–89.9 %), 65.7 % (95CI 60.1–71.4 %), 42.4 % (95CI 32.2–52.6 %) and 21.4 % (95CI 15.3–27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1–9.3 %), hypertension was 15.6 % (95CI 12.6–18.6 %), cardiovascular disease was 4.7 % (95CI 3.1–6.2 %), and malignancy was 1.2 % (95CI 0.5–1.8 %). The complications, including ARDS risk, ranged from 5.6–13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7–10.8 %), AKI at 2.1 % (95CI 0.6–3.7 %), and shock at 4.7 % (95CI 0.9–8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0–61.9 %) and 41.7 % (95CI 26.4–56.9 %), respectively. Conclusion Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.

negative: CO.ME.T.A. -- covid-19 media textual analysis. A dashboard for media monitoring The focus of this paper is to trace how mass media, particularly newspapers, have addressed the issues about the containment of contagion or the explanation of epidemiological evolution. We propose an interactive dashboard: CO.ME.T.A.. During crises it is important to shape the best communication strategies in order to respond to critical situations. In this regard, it is important to monitor the information that mass media and social platforms convey. The dashboard allows to explore the mining of contents extracted and study the lexical structure that links the main discussion topics. The dashboard merges together four methods: text mining, sentiment analysis, textual network analysis and latent topic models. Results obtained on a subset of documents show not only a health-related semantic dimension, but it also extends to social-economic dimensions.

negative: COVID-19: Immunology and treatment options Abstract The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

negative: Temporal rise in the proportion of younger adults and older adolescents among coronavirus disease (COVID-19) cases following the introduction of physical distancing measures, Germany, March to April 2020 Using data on coronavirus disease (COVID-19) cases in Germany from the Robert Koch Institute, we found a relative increase with time in the prevalence in 15–34 year-olds (particularly 20–24-year-olds) compared with 35–49- and 10–14-year-olds (we excluded older and younger ages because of different healthcare seeking behaviour). This suggests an elevated role for that age group in propagating the epidemic following the introduction of physical distancing measures.

negative: Clinical Outcomes in COVID‐19 Patients Treated with Tocilizumab: An Individual Patient Data Systematic Review BACKGROUND: Current evidence suggests an important role of interleukin‐6 (IL‐6) pathway in SARS‐CoV‐2‐related cytokine release storm in severely ill COVID‐19 patients. Inhibition of the IL‐6 pathway with tocilizumab has been employed successfully in some of these patients but the data is mostly consistent of case reports and series. METHODS: We performed a systematic search of PubMed, Embase, and Medline from 22(nd) April 2020 and again on 27(th) April 2020 using the following search terms alone or in combination: “COVID‐19”, “coronavirus”, “SARS‐CoV‐2”, “COVID”, “anti‐interleukin 6 receptor antibodies”, “anti‐IL‐6”, “tocilizumab”, “sarilumab”, “siltuximab”. We included studies which reported individual patient data. We extracted and analyzed individual level data on baseline characteristics, laboratory findings, and clinical outcomes. Primary endpoint was in‐hospital mortality. Secondary endpoints included in‐hospital complications, recovery rates, effect of patient characteristics on the primary outcome and changes in levels of inflammatory markers. RESULTS: 352 records were identified through the systematic search of which 10 studies met the inclusion criteria. A single study currently under review was also added. Eleven observational studies encompassing 29 patients were included in the present review. There were more males (24 [82.8%]) and hypertension was the most common comorbidity (16 [48.3 %]). Over an average of 5.4 hospital days, the primary endpoint occurred in 6 (20.7%) patients. Among surviving patients, about 10% had worsened disease and 17% recovered. The most common complication was acute respiratory distress syndrome (8[27.6%]). IL‐6 level was significantly higher after the initiation of tocilizumab with median (IQR) of 376.6 (148‐900.6) pg/mL compared to the baseline of 71.1 (31.9‐122.8) pg/mL (p=0.002). Mean (SD) levels of c‐reactive protein (CRP) were significantly decreased following treatment 24.6 (26.9) mg/L compared to baseline 140.4 (77) mg/L (P< 0.0001). Baseline demographics were not significantly different amongst survivors and non‐survivors by Fisher's exact test. CONCLUSION: In COVID‐19 patients treated with tocilizumab, IL‐6 levels are significantly elevated which are supportive of cytokine storm. Following initiation of tocilizumab, there is elevation in the IL‐6 levels and CRP levels dramatically decrease suggesting an improvement in this hyper‐inflammatory state. Ongoing randomized control trials will allow for further evaluation of this promising therapy. IMPORTANCE: Recent data indicate that severe COVID 19 causes cytokine release storm and is associated with worse clinical outcomes and IL‐6 plays an important role. It is suggestive that anti‐IL6 results in the improvement of this hyperinflammatory state. However, to our knowledge, there is no individual patient data systematic review performed to summarize baseline characteristics and clinical outcomes of COVID 19 patients who received tocilizumab. This article is protected by copyright. All rights reserved.

negative: COVID‐19: Moving beyond the pandemic Severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV‐2) is the cause of COVID‐19. As of April 11th, 2020, there were almost 2 million cases of COVID‐19 internationally and over 100,000 deaths (John Hopkins University, 2020). There has been significant effort to increase hospital and healthcare capacity to reduce the number of fatalities associated with this global pandemic (Choi & Logsdon 2020).

negative: Effectiveness of convalescent plasma therapy in severe COVID-19 patients Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10(9)/L vs. 0.76 × 10(9)/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

negative: Post-COVID-19 global health strategies: the need for an interdisciplinary approach For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach--coordinated by geriatrician--to cope the potential post-acute care needs of recovered COVID-19 patients.

negative: Early Impact of COVID-19 on Individuals with Eating Disorders: A survey of ~1000 Individuals in the United States and the Netherlands We received rapid ethical permission to evaluate the early impact of COVID-19 on people with eating disorders. Participants in the United States (US, N=511) and the Netherlands (NL, N=510), recruited through ongoing studies and social media, completed an online baseline survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with diagnoses. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover.

negative: Tachycardia amongst subjects recovering from severe acute respiratory syndrome (SARS) Abstract SARS is a new infection in human. Patients recovering from SARS had palpitation in the form of sinus tachycardia. This study to identify the possible causes for the tachycardia excluded active disease, thyroid dysfunction, haematological, cardiac, autonomic and significant pulmonary defect at 2 months from onset of disease. The symptomatology was attributed to physical deconditioning and anxiety state. Physical and psychological fitness should be restored with rehabilitation.

negative: A Review of Neurological Complications of COVID-19 The SARS-CoV-2, a novel virus has shown an association with central nervous system (CNS) symptoms. Initial retrospective studies emerging from China and France, as well as case reports from different parts of the world revealed a spectrum of neurological symptoms ranging from a simple headache to more serious encephalitis and dysexecutive syndromes. Authors have tried to explain this neurotropism of the virus by comparing invasion mechanisms with prior epidemic coronavirus like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Concrete evidence on those viruses has been limited. This review attempts to discuss various pathophysiological mechanisms as it relates to neurological complications of SARS-CoV-2. We will also discuss the neurological manifestations seen in various retrospective studies, systemic reviews, and case reports.

negative: Metapneumovirus Infections and Respiratory Complications Acute respiratory tract infections (ARTIs) are the most common illnesses experienced by people of all ages worldwide. In 2001, a new respiratory pathogen called human metapneumovirus (hMPV) was identified in respiratory secretions. hMPV is an RNA virus of the Paramyxoviridae family, and it has been isolated on every continent and from individuals of all ages. hMPV causes 7 to 19% of all cases of ARTIs in both hospitalized and outpatient children, and the rate of detection in adults is approximately 3%. Symptoms of hMPV infection range from a mild cold to a severe disease requiring a ventilator and cardiovascular support. The main risk factors for severe disease upon hMPV infection are the presence of a high viral load, coinfection with other agents (especially human respiratory syncytial virus), being between 0 and 5 months old or older than 65 years, and immunodeficiency. Currently, available treatments for hMPV infections are only supportive, and antiviral drugs are employed in cases of severe disease as a last resort. Ribavirin and immunoglobulins have been used in some patients, but the real efficacy of these treatments is unclear. At present, the direction of research on therapy for hMPV infection is toward the development of new approaches, and a variety of vaccination strategies are being explored and tested in animal models. However, further studies are required to define the best treatment and prevention strategies.

negative: Ethical issues related to the hydroxychloroquine treatment prescription for Covid-19 Abstract The 2019-20 coronavirus pandemic (COVID-19), has led to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, no drugs have demonstrated safety and efficacy in randomized controlled trials for patients with COVID-19. Although the association between Hydroxychloroquine and Azithromycin efficacy lack of solid evidence-base, several governments have adopted it for all virology confirmed Covid-19 cases even for those who are asymptomatic. In the following, we aim to discuss some of the ethical issues associated with the use of this treatment association. We mainly tried to discuss the following controversial questions: Is it ethical not to treat a patient while a treatment exists and is used for other indications than Covid-19 for which it’s not proven yet? If yes, is a randomized controlled trial to prove the hydroxychloroquine for the Covid-19 treatment, necessary, in the context of covid-19 pandemic? If No, is it the government’s right to decide the hydroxychloroquine treatment for all covid-19 patients? and what should be the physicians’ attitudes? Finally, what are the government, physicians, and patient’s rights and responsibilities? The paper conclude that, since health authorities in some countries recommended this off-label use treatment, physicians are challenged by the requirement of veracity while providing care to their patients and the implications of such a requirement; they are facing the challenge of balancing this guideline and their own conviction. Furthermore, the fundamental principles of beneficence and non-maleficence, and respect for persons should underlie any reflection process to address this dilemma. In addition, in a pandemic context, the limits between the government’s, practitioner’s and patient’s rights and obligations are not clear which could significantly endanger the universal ethical principles in clinical practice. It could also undermine any attempt to develop serious clinical trials to prove the considered off-label drug.

negative: Persistent Airway Obstruction After Virus Infection Is Not Associated With Airway Inflammation Abstract Background:This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. Methods:Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. Results:Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1percent predicted [Δ%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Δ%FEV1, ≥ 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. Conclusion:Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.

negative: The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources – Wikipedia, the GDELT Project and the Internet Archive – to quantify population-scale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geolocalized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks.

negative: Evidence and characteristics of human-to-human transmission of SARS-CoV-2 Background: On December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.

negative: A Stratified Model to Quantify the Effects of Containment Policies on the Spread of COVID-19 The SARS-Cov-2 virus is spreading fast all over the world and has already imposed a significant social and economic cost in many countries. Different countries have utilised a variety of containment policies with an emphasis on social distancing as a strategy to stop the spread of COVID-19. Quantifying the effects of such policies in different time-scales and comparing the efficacy of various available policies is of utmost importance for policy-makers in different countries. That is even more important when the policy-makers want to plan for long-term strategies and to weigh each option based on its epidemiological effects and socio-economic costs. In the absence of detailed knowledge of the interactions between individuals in a population and the characteristics of the SARS-Cov-2 virus, quantifying the effects of these policies is very difficult. Hence, there is an immediate need for models that can predict the spread of COVID-19 in a population, without the need for such detailed information. In this manuscript, a method is presented that can be used to predict the spread of COVID-19 in any country and under any containment policy imposed separately on different groups in the population. The method tunes the parameters of a known stratified model based on the available data on the spread of COVID-19. The model includes a set of nonlinear ordinary differential equations and is easy to simulate and easy to understand. As it is presented in this manuscript, the population is divided into age-groups. But given the availability of the data, there is no reason to limit the stratification into only age-groups and we can consider any relevant groups. To estimate the parameters of the model such that it reflects the characteristics of the spread of COVID-19 in a population, the method relies on an optimisation scheme. More specifically, the optimisation scheme estimates the contact rates between different age groups in the population. But a very important and useful feature of the model is that the estimated parameters for one population can be translated and used for any other population with a known age-structure, which in this day and age, includes almost any country or city in the world. Also, it is shown that the method is quite insensitive to the underlying assumptions in the optimisation scheme and also to deliberate or non-deliberate errors that might have occurred in collecting the data. The capabilities of the model are demonstrated using a case study under different containment policies, from an uncontained population to mitigation and suppression policies. Also, we can use the model to quantify the effects of strategies which include switching between different containment policies at pre-determined points in time. The model allows us to quantify the effects of each of these policies on the spread of the disease in a population, in particular, the instantaneous and total numbers of infectious individuals in a population which are important parameters for policy-makers. The simulation results, as explained in the following, provide some insight into various policies and some of the results are possibly counter-intuitive for many people. For example, the model predicts that closing down schools and universities without any other containment policy imposed on older age-groups has almost no impact on the number of patients that might need support-care in hospitals. The method provides an easy-to-use tool to use the information collected on the spread of COVID-19 in a country or region and then use that information in another population which might not have been as widely affected by the disease yet.

negative: COVID-19 Tragic Pandemic: Concerns over Unintentional “Directed Accelerated Evolution” of Novel Coronavirus (SARS-CoV-2) and Introducing a Modified Treatment Method for ARDS Global health authorities are trying to work out the current status of the novel coronavirus (COVID-19) outbreak and explore methods to reduce the rate of its transmission to healthy individuals. In this viewpoint we provide insights concerning how health care professionals can unintentionally shift the novel coronavirus type to more drug-resistant forms. It is worth noting that viruses usually have different sensitivities to physical and chemical damaging agents such antiviral drugs, UV and heat ranging from extremely sensitive (ES) to extremely resistant (ER) based on a bell-shaped curve. Given this consideration, the widespread infection of people with such ER viruses would be a real disaster. Here, we introduce a modified treatment method for COVID-19-associated pneumonia. In this proposed method, COVID-19 patients will receive a single dose of 100, 180 or 250 mSv X-ray radiation that is less than the maximum annual radiation dose of the residents of high background radiation areas of Ramsar that is up to 260 mSv. In contrast with antiviral drugs, a single dose of either 100, 180 or 250 mSv of low LET X-rays cannot exert a significant selective pressure on the novel coronavirus (SARS-CoV-2) and hence does not lead to directed accelerated evolution of these viruses. Moreover, Low Dose Radiation (LDR) has the capacity of modulating excessive inflammatory responses, regulating lymphocyte counts, and controling bacterial co-infections in patients with COVID-19.

negative: Coronavirus envelope (E) protein remains at the site of assembly Abstract Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly.

negative: Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic review Importance: In 2002-2003, a severe pulmonary infectious disease occurred in Guangdong, China. The disease was caused by SARS-CoV, 17 years apart, also happen in China, and SARS-CoV-2, this epidemic has posed a significant hazard to people health both China and the whole world. Objective: Summarized the latest epidemiological changes, clinical manifestations, auxiliary examination and pathological characteristics of COVID-19. Evidence Review: PubMed database were searched from 2019 to 2020 using the index terms novel coronavirus or COVID-19 or 2019-nCoV or SARS-CoV-2 and synonyms. Articles that reported clinical characteristics, laboratory results, imageological diagnosis and pathologic condition were included and were retrospectively reviewed for these cases. This paper adopts the method of descriptive statistics. Results: 34 COVID-19-related articles were eligible for this systematic review;Four of the articles were related to pathology. We found that Fever (86.0%), cough (63.9%) and Malaise/Fatigue (34.7%) were the most common symptoms in COVID-19. But in general, the clinical symptoms and signs of COVID-19 were not obvious. Compared with SARS, COVID-19 was transmitted in a more diverse way. The mortality rates of COVID-19 were 2.5%, and the overall infection rate of healthcare worker of COVID-19 was 3.9%. We also found that the pathological features of COVID-19 have greatly similar with SARS, which manifested as ARDS. But the latest pathological examination of COVID-19 revealed the obvious mucinous secretions in the lungs. Interpretation: The clinical and pathological characteristics of SARS and COVID-19 in China are very similar, but also difference. The latest finds of pathological examination on COVID-19 may upend existing treatment schemes, so the early recognition of disease by healthcare worker is very important.

negative: Vaccine Rationing and the Urgency of Social Justice in the Covid‐19 Response The Covid‐19 pandemic needs to be considered from two perspectives simultaneously. First, there are questions about which policies are most effective and fair in the here and now, as the pandemic unfolds. These polices concern, for example, who should receive priority in being tested, how to implement contact tracing, or how to decide who should get ventilators or vaccines when not all can. Second, it is imperative to anticipate the medium‐ and longer‐term consequences that these policies have. The case of vaccine rationing is particularly instructive. Ethical, epidemiological, and economic reasons demand that rationing approaches give priority to groups who have been structurally and historically disadvantaged, even if this means that overall life years gained may be lower.

negative: Applicability of time fractional derivative models for simulating the dynamics and mitigation scenarios of COVID-19 Fractional calculus provides a promising tool for modeling fractional dynamics in computational biology, and this study tests the applicability of fractional-derivative equations (FDEs) for modeling the dynamics and mitigation scenarios of the novel coronavirus for the first time. The coronavirus disease 2019 (COVID-19) pandemic radically impacts our lives, while the evolution dynamics of COVID-19 remain obscure. A time-dependent Susceptible, Exposed, Infectious, and Recovered (SEIR) model was proposed and applied to fit and then predict the time series of COVID-19 evolution observed over the last three months (up to 3/22/2020) in China. The model results revealed that 1) the transmission, infection and recovery dynamics follow the integral-order SEIR model with significant spatiotemporal variations in the recovery rate, likely due to the continuous improvement of screening techniques and public hospital systems, as well as full city lockdowns in China, and 2) the evolution of number of deaths follows the time FDE, likely due to the time memory in the death toll. The validated SEIR model was then applied to predict COVID-19 evolution in the United States, Italy, Japan, and South Korea. In addition, a time FDE model based on the random walk particle tracking scheme, analogous to a mixing-limited bimolecular reaction model, was developed to evaluate non-pharmaceutical strategies to mitigate COVID-19 spread. Preliminary tests using the FDE model showed that self-quarantine may not be as efficient as strict social distancing in slowing COVID-19 spread. Therefore, caution is needed when applying FDEs to model the coronavirus outbreak, since specific COVID-19 kinetics may not exhibit nonlocal behavior. Particularly, the spread of COVID-19 may be affected by the rapid improvement of health care systems which may remove the memory impact in COVID-19 dynamics (resulting in a short-tailed recovery curve), while the death toll and mitigation of COVID-19 can be captured by the time FDEs due to the nonlocal, memory impact in fatality and human activities.

negative: Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19 BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving ≥1 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.

negative: COVID-19: Development of a robust mathematical model and simulation package with consideration for ageing population and time delay for control action and resusceptibility The current global health emergency triggered by the pandemic COVID-19 is one of the greatest challenges mankind face in this generation. Computational simulations have played an important role to predict the development of the current pandemic. Such simulations enable early indications on the future projections of the pandemic and is useful to estimate the efficiency of control action in the battle against the SARS-CoV-2 virus. The SEIR model is a well-known method used in computational simulations of infectious viral diseases and it has been widely used to model other epidemics such as Ebola, SARS, MERS, and influenza A. This paper presents a modified SEIRS model with additional exit conditions in the form of death rates and resusceptibility, where we can tune the exit conditions in the model to extend prediction on the current projections of the pandemic into three possible outcomes; death, recovery, and recovery with a possibility of resusceptibility. The model also considers specific information such as ageing factor of the population, time delay on the development of the pandemic due to control action measures, as well as resusceptibility with temporal immune response. Owing to huge variations in clinical symptoms exhibited by COVID-19, the proposed model aims to reflect better on the current scenario and case data reported, such that the spread of the disease and the efficiency of the control action taken can be better understood. The model is verified using two case studies for verification and prediction studies, based on the real-world data in South Korea and Northern Ireland, respectively.

negative: 250 examens de laboratoire en pratique médicale courante

negative: Revisión Narrativa Sobre La Respuesta Inmunitaria Frente A Coronavirus: Descripción General, Aplicabilidad Para Sars-Cov2 E Implicaciones Terapéuticas Abstract The new coronavirus (SARS-CoV2) that causes a severe acute respiratory syndrome emerged in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and it applicability to SARS-CoV2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments.

negative: Analyzing the epidemiological outbreak of COVID‐19: A visual exploratory data analysis approach There is an obvious concern globally regarding the fact about the emerging coronavirus 2019 novel coronavirus (2019‐nCoV) as a worldwide public health threat. As the outbreak of COVID‐19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China, caused by the SARS‐CoV‐2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this study, we present an effort to compile and analyze epidemiological outbreak information on COVID‐19 based on the several open datasets on 2019‐nCoV provided by the Johns Hopkins University, World Health Organization, Chinese Center for Disease Control and Prevention, National Health Commission, and DXY. An exploratory data analysis with visualizations has been made to understand the number of different cases reported (confirmed, death, and recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information to begin the evaluation necessary to understand the risks and begin containment activities.

negative: Coronavirus Goes Viral: Quantifying the COVID-19 Misinformation Epidemic on Twitter Background Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic, misinformation has been spreading uninhibited over traditional and social media at a rapid pace. We sought to analyze the magnitude of misinformation that is being spread on Twitter (Twitter, Inc., San Francisco, CA) regarding the coronavirus epidemic. Materials and methods We conducted a search on Twitter using 14 different trending hashtags and keywords related to the COVID-19 epidemic. We then summarized and assessed individual tweets for misinformation in comparison to verified and peer-reviewed resources. Descriptive statistics were used to compare terms and hashtags, and to identify individual tweets and account characteristics. Results The study included 673 tweets. Most tweets were posted by informal individuals/groups (66%), and 129 (19.2%) belonged to verified Twitter accounts. The majority of included tweets contained serious content (91.2%); 548 tweets (81.4%) included genuine information pertaining to the COVID-19 epidemic. Around 70% of the tweets tackled medical/public health information, while the others were pertaining to sociopolitical and financial factors. In total, 153 tweets (24.8%) included misinformation, and 107 (17.4%) included unverifiable information regarding the COVID-19 epidemic. The rate of misinformation was higher among informal individual/group accounts (33.8%, p: <0.001). Tweets from unverified Twitter accounts contained more misinformation (31.0% vs 12.6% for verified accounts, p: <0.001). Tweets from healthcare/public health accounts had the lowest rate of unverifiable information (12.3%, p: 0.04). The number of likes and retweets per tweet was not associated with a difference in either false or unverifiable content. The keyword “COVID-19” had the lowest rate of misinformation and unverifiable information, while the keywords “#2019_ncov” and “Corona” were associated with the highest amount of misinformation and unverifiable content respectively. Conclusions Medical misinformation and unverifiable content pertaining to the global COVID-19 epidemic are being propagated at an alarming rate on social media. We provide an early quantification of the magnitude of misinformation spread and highlight the importance of early interventions in order to curb this phenomenon that endangers public safety at a time when awareness and appropriate preventive actions are paramount.

negative: Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1 (Review Article) The Coronavirus (COVID-19) pandemic has resulted in over 2.3 million confirmed cases and over 160,000 deaths. The impact of COVID-19 on surgical practice is widespread ranging from workforce and staffing issues, procedural prioritisation, viral transmission risk intraoperatively, changes to perioperative practice and ways of working alongside the impact on surgical education and training. Whilst there has been a growing literature base describing the early clinical course of COVID-19 and on aspects of critical care related to treating these patients, there has been a dearth of evidence on how this pandemic will affect surgical practice. This paper seeks to review the current evidence and offers recommendations for changes to surgical practice to minimise the effect of the COVID-19 pandemic.

negative: Two distinct cases with COVID‐19 in kidney transplant recipients The fatality of novel coronavirus disease 2019 (COVID‐19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID‐19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36‐year‐old man who underwent KT 3 years ago. He was diagnosed with COVID‐19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID‐19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug‐to‐drug interaction. The second case was developed in a 56‐year‐old man without any symptoms. He received a second KT from an ABO‐incompatible donor 8 years ago. He was diagnosed with COVID‐19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.

negative: A national prospective cohort study of SARS/COV2 pandemic outcomes in the U.S.: The CHASING COVID Cohort Introduction: The Chasing COVID Cohort (C3) study is a US-based, geographically and socio-demographically diverse sample of adults (18 and older) enrolled into a prospective cohort study during the upswing of the U.S. COVID-19 pandemic. Methods: We used internet-based strategies to enroll C3 participants beginning March 28th, 2020. Following baseline questionnaire completion, study participants will be contacted monthly (for 6 months) to complete assessments of engagement in non-pharmaceutical interventions (e.g., use of cloth masks, avoiding large gatherings); COVID-19 symptoms; SARS/COV2 testing and diagnosis; hospitalizations; healthcare access; and uptake of health messaging. Dried blood spot (DBS) specimens will be collected at the first follow-up assessment (last week of April 2020) and at month 3 (last week of June 2020) and stored until a validated serologic test is available. Results: As of April 20, 2020, the number of people that completed the baseline survey and provided contact information for follow-up was 7,070. Participants resided in all 50 US states, the District of Columbia, Puerto Rico, and Guam. At least 24% of participants were frontline workers (healthcare and other essential workers). Twenty-three percent (23%) were 60+ years, 24% were Black or Hispanic, 52% were men, and 52% were currently employed. Nearly 20% reported recent COVID-like symptoms (cough, fever or shortness of breath) and a high proportion reported engaging in non-pharmaceutical interventions that reduce SARS/COV2 spread (93% avoided groups >20, 58% wore masks; 73% quarantined). More than half (54%) had higher risk for severe COVID-19 illness should they become infected with SARS/COV2 based on age, underlying health conditions (e.g., chronic lung disease), or daily smoking. Discussion: A geographically and socio-demographically diverse group of participants was rapidly enrolled in the C3 during the upswing of the SARS/COV2 pandemic. Strengths of the C3 include the potential for direct observation of, and risk factors for, seroconversion and incident COVID disease (among those with or without antibodies to SARS/COV2) in areas of active transmission.

negative: Releasing the lockdown in the UK Covid-19 epidemic: a stochastic model Abstract Background In a classic epidemic, the infected population has an early exponential phase, before slowing and fading to its peak. Mitigating interventions may change the exponent during the rising phase and a plateau can replace a peak. With interventions comes the risk that relaxation causes a second-wave. In the UK Covid-19 epidemic, infections cannot be counted, but their influence is seen in the curve of the mortality data. This work simulated social distancing and the lockdown in the UK Covid-19 epidemic to explore strategies for relaxation. Methods Cumulative mortality data was transposed 20 days earlier to identify three doubling periods separated by the 17th March - social distancing, and 23rd March - lockdown. A set of stochastic processes simulated viral transmission between interacting individuals using Covid-19 incubation and illness durations. Social distancing and restrictions on interactions were imposed and later relaxed. Principal Findings Daily mortality data, consistent with that seen in the UK Covid-19 epidemic to 24th April 2020 was simulated. This output predicts that under a lockdown maintained till early July 2020, UK deaths will exceed 31,000, but leave a large susceptible population and a requirement for vaccination or quarantine. An earlier staged relaxation carries a risk of a second-wave. The model allows exploration of strategies for lifting the lockdown. Interpretation Social distancing and the lockdown have had an impressive impact on the UK Covid-19 epidemic and saved lives, caution is now needed in planning its relaxation.

negative: Recurrence of COVID-19 after recovery: a case report from Italy

negative: Effects of latency and age structure on the dynamics and containment of COVID-19 In this paper we develop an SEIR-type model of COVID-19, with account for two particular aspects: non-exponential distribution of incubation and recovery periods, as well as age structure of the population. For the mean-field model, which does not distinguish between different age groups, we demonstrate that including a more realistic Gamma distribution of incubation and recovery periods may not have an effect on the total number of deaths and the overall size of an epidemic, but it has a major effect in terms of increasing the peak numbers of infected and critical care cases, as well as on changing the timescales of an epidemic, both in terms of time to reach the peak, and the overall duration of an outbreak. In order to obtain more accurate estimates of disease progression and investigate different strategies for introducing and lifting the lockdown, we have also considered an age-structured version of the model, which has allowed us to include more accurate data on age-specific rates of hospitalisation and COVID-19 related mortality. Applying this model to three comparable neighbouring regions in the UK has delivered some fascinating insights regarding the effect of quarantine in regions with different population structure. We have discovered that for a fixed quarantine duration, the timing of its start is very important in the sense that the second epidemic wave after lifting the quarantine can be significantly smaller or larger depending on the specific population structure. Also, the later the fixed-duration quarantine is introduced, the smaller is the resulting final number of deaths at the end of the outbreak. When the quarantine is introduced simultaneously for all regions, increasing quarantine duration postpones and slightly reduces the epidemic peak, though without noticeable differences in peak magnitude between different quarantine durations.

negative: Temporary Immunity and Multiple Waves of COVID-19 In this work we use mathematical modeling to describe the potential phenomena which may occur if immunity to COVID-19 lasts for a finite time instead of being permanent, i.e. if a recovered COVID-19 patient may again become susceptible to the virus after a given time interval following his/her recovery. Whether this really happens or not is unknown at the current time. If it does happen, then we find that for certain combinations of parameter values (social mobility, contact tracing, immunity threshold duration etc), the disease can keep recurring in wave after wave of outbreaks, with a periodicity approximately equal to twice the immunity threshold. Such cyclical attacks can be prevented trivially if public health interventions are strong enough to contain the disease outright. Of greater interest is the finding that should such effective interventions not prove possible, then also the second and subsequent waves can be forestalled by a consciously relaxed intervention level which finishes off the first wave before the immunity threshold is breached. Such an approach leads to higher case counts in the immediate term but significantly lower counts in the long term as well as a drastically shortened overall course of the epidemic.

negative: Economic Recovery Following the COVID-19 Pandemic: Resuming Elective Orthopaedic Surgery and Total Joint Arthroplasty BACKGROUND: The economic effects of the COVID-19 crisis are not like anything the U.S. health care system has ever experienced. METHODS: As we begin to emerge from the peak of the COVID-19 pandemic, we need to plan the sustainable resumption of elective procedures. We must first ensure the safety of our patients and surgical staff. It must be a priority to monitor the availability of supplies for the continued care of patients suffering from COVID-19. As we resume elective orthopedic surgery and total joint arthroplasty, we must begin to reduce expenses by renegotiating vendor contracts, use ambulatory surgery centers and hospital outpatient departments in a safe and effective manner, adhere to strict evidence-based and COVID-19–adjusted practices, and incorporate telemedicine and other technology platforms when feasible for health care systems and orthopedic groups to survive economically. RESULTS: The return to normalcy will be slow and may be different than what we are accustomed to, but we must work together to plan a transition to a more sustainable health care reality which accommodates a COVID-19 world. CONCLUSION: Our goal should be using these lessons to achieve a healthy and successful 2021 fiscal year.

negative: Clearance and Persistence of SARS‐CoV‐2 RNA in COVID‐19 patients COVID‐19 patients may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the SARS‐CoV‐2 viral clearance profile is crucial to establish a re‐testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS‐CoV‐2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative RT‐PCR tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT‐PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than two weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead. This article is protected by copyright. All rights reserved.

negative: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.

negative: When COVID-19 will decline in India? Prediction by combination of recovery and case load rate BACKGROUND: The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020. There is sudden need of statistical modeling due to onset of COVID-19 pandemic across the world. But health planning and policy requirements need the estimates of disease problem from clinical data. OBJECTIVE: The present study aimed to predict the declination of COVID-19 using recovery rate and case load rate on basis of available data form India. METHODS: The reported COVID-19 cases in the country were obtained from website (https://datahub.io/core/covid-19#resource-covid-19_zip/). The confirmed cases, recovered cases and deaths were used for estimating recovery rate, case load rate and death rate till date June 04, 2020. RESULTS: A total of 216919 confirmed cases were reported nationwide in India on June 04, 2020. It is found that the recovery rate increased to 47.99% and case load rate decreased to 49.21%. Death rate is found to be very low 2.80%. Accordingly, coincidence of the difference of cases load rate and recovery rate (delta) will reveal a declination in expected COVID-19 cases. CONCLUSION: The epidemic in the country was mainly caused by the movement of people from various foreign countries to India. Lockdown as restricting the migration of population and decision taken by the government to quarantine the population may greatly reduce the risk of continued spread of the epidemic in India. This study predicts that when the case load rate gets lesser than recovery rate, there after COVID-19 patients would be started to decline.

negative: Imagerie moderne des pneumonies infectieuses aiguës The acute infectious pneumonia constitute a problem of public health because they are one cause of great morbidity and mortality in adult. If the clinical and radiological information allow often to achieve the diagnosis of infectious pneumonia, the etiologic diagnosis is more difficult. Indeed, numerous pathogen germs are responsible of pneumonia and the reaction of lung is not very various, this explain the low specificity of radiological imaging, except for few characteristic cases. That’s why the understanding of physiopathologic mechanisms allow to explain some special cases. In the same way, the knowledge of anatomical and radiological understanding allow the acknowledgment of three main radiographic appearance. As for the evaluation of epidemiological and immune contexte, they can allow to recognize the concern germ.

negative: Age Pattern of Premature Mortality under varying scenarios of COVID-19 Infection in India Background India is vulnerable to community infection of COVID-19 due to crowded and poor living condition, high density, slums in urban areas and poor health care system. The number of COVID-19 infection has crossed 120,000 with over 3500 deaths despite a prolonged period of lockdown and restrictions in public spaces. Given the likely scale and magnitude of this pandemic, this is a modest attempt to assess its impact on the age pattern of mortality under the varying scenarios. Data and Methods Data from the Sample Registration System (SRS), covid19india.org and country-specific data from worldmeter are used in the analysis. Descriptive statistics, case fatality ratio, case fatality ratio with 14 days delay, abridged life table, years of potential life lost (YPLL), disability-adjusted life years (DALY) are used. Results The case fatality ratio (CFR) with 14 days delay for India is at least twice higher (8.0) than CFR of 3.4. Considering 8% mortality rate rate and varying scenarios of community infection by 0.5%, 1% and 2%, India's life expectancy will reduce by 0.8, 1.5 and 3.0 years and potential life lost by 12.1 million, 24.3 million and 48.6 million years respectively. A community infection of 0.5% may result in DALY by 6.2 per 1000 population. Major share of PYLL and DALY is accounted for the working ages. Conclusion COVID-19 has a visible impact on mortality with loss of productive life years in working ages. The sustained effort at containing the transmission at each administrative unit is recommended to arrest mortality owing by the working ages. Key Words: COVID-19, life expectancy, mortality, premature, DALY, India

negative: Detection of Covid-19 From Chest X-ray Images Using Artificial Intelligence: An Early Review In 2019, the entire world is facing a situation of health emergency due to a newly emerged coronavirus (COVID-19). Almost 196 countries are affected by covid-19, while USA, Italy, China, Spain, Iran, and France have the maximum active cases of COVID-19. The issues, medical and healthcare departments are facing in delay of detecting the COVID-19. Several artificial intelligence based system are designed for the automatic detection of COVID-19 using chest x-rays. In this article we will discuss the different approaches used for the detection of COVID-19 and the challenges we are facing. It is mandatory to develop an automatic detection system to prevent the transfer of the virus through contact. Several deep learning architecture are deployed for the detection of COVID-19 such as ResNet, Inception, Googlenet etc. All these approaches are detecting the subjects suffering with pneumonia while its hard to decide whether the pneumonia is caused by COVID-19 or due to any other bacterial or fungal attack.

negative: ElaD, a Deubiquitinating Protease Expressed by E. coli BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan.

negative: Extracorporeal Membrane Oxygenation – Crucial Considerations during the Coronavirus Crisis

negative: ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection In December 2019 and January 2020, novel coronavirus (2019-nCoV) - infected pneumonia (NCIP) occurred in Wuhan, and has already posed a serious threat to public health. ACE2 (Angiotensin Converting Enzyme 2) has been shown to be one of the major receptors that mediate the entry of 2019-nCoV into human cells, which also happens in severe acute respiratory syndrome coronavirus (SARS). Several researches have indicated that some patients have abnormal renal function or even kidney damage in addition to injury in respiratory system, and the related mechanism is unknown. This arouses our interest in whether coronavirus infection will affect the urinary and male reproductive systems. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicate that ACE2 highly expresses in renal tubular cells, Leydig cells and cells in seminiferous ducts in testis. Therefore, virus might directly bind to such ACE2 positive cells and damage the kidney and testicular tissue of patients. Our results indicate that renal function evaluation and special care should be performed in 2019-nCoV patients during clinical work, because of the kidney damage caused by virus and antiviral drugs with certain renal toxicity. In addition, due to the potential pathogenicity of the virus to testicular tissues, clinicians should pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.

negative: Mass gathering events and reducing further global spread of COVID-19: a political and public health dilemma

negative: Novel coronavirus: From discovery to clinical diagnostics Abstract A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.

negative: Recovery from Infection This chapter discusses the immunological factors associated in the recovery of host from infections. Antibody, T cells, natural killer cells, complement, phagocytes, and interferon are involved in the response to nearly all infections and, without any doubt, are together responsible for recovery. There is good evidence that T-cell-mediated immunity is of supreme importance in recovery from a variety of microbial infections. These are the infections in which the microorganism replicates intracellularly. Tissue responses in the host bear the hallmarks of T-cell involvement, the infiltrating cells consisting primarily of lymphocytes and macrophages. Inflammation, whether induced by immunological reactions, tissue damage or microbial products, plays a vital role in recovery from infection. Inflammation is necessary for the proper functioning of the immune defenses because it focuses all circulating antimicrobial factors onto the site of infection. Complement can carry out antimicrobial activities. However, there is little direct evidence that the antimicrobial activities of complement are in fact important in the body. Interferons also act on uninfected cells, binding to a cell surface receptor and activating a number of genes involved in immunity to viruses. Multimechanistic recovery is illustrated in the chapter and other issues, such as the role of temperature, tissue repair, and resistance to re-infection are discussed.

negative: COVID‐19 in Spain: Transplantation in the midst of the pandemic Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.

negative: Self-Interest versus Group-Interest in Antiviral Control Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.

negative: COVID-19, Mental Health and Aging: A Need for New Knowledge to Bridge Science and Service

negative: A picture of the covid-19 impact on IVIRMA fertility treatment clinics in Spain and Italy Abstract The emergence of the novel coronavirus infection that arose in Wuhan, China in December 2019 has resulted in an epidemic that has quickly expanded to become one of the most significant public health threats in recent times. Unfortunately, the disease has spread globally. On March 11th (2020) World Health Organization (WHO) declared Covid-19 a pandemic and has called governments to take urgent and aggressive action to change the course of the outbreak. Within the context of Assisted Reproduction, both reproductive medicine professionals and patients are also fighting against this unprecedented viral pandemic. In view of events, most of us had to make serious decisions, some of them with a lack of scientific evidence due to the circumstances and with the only objective of ensuring the safe care of our patients, reduce non-essential contacts and prevent possible maternal and fetal complications in future pregnancies. Pregnant women should not be considered at high risk for developing severe infection. Up to date, there are no reported deaths in pregnant women with Covid-19, while in the cases that have presented pneumonia because of Covid-19, the symptoms have been moderate and with a good prognosis in recovery

negative: Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020 Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717–459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250–67,632) patients requiring intensive care. Aggressive containment strategies are required.

negative: Global research trends of World Health Organization’s top eight emerging pathogens BACKGROUND: On December 8(th), 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine – related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

negative: Literature-based review of the drugs used for the treatment of COVID-19 COVID-19 is primarily a respiratory disease caused by a newly discovered SARS-CoV-2 virus and identified in the city of Wuhan, China in December 2019. WHO has declared this disease as a pandemic, and warned other countries. Presently this has affected 216 countries, areas or territories worldwide, spreading of this disease is very fast in USA, Brazil, and Russia than in the country of its origin, China. Like other coronaviruses, this may develop respiratory tract infections in the patients range from mild to fatal illness like pneumonia and acute respiratory distress syndrome (ARDS). As of now, no effective drug, vaccine, or any procedure is available and experiments are underway. However, empirical therapy is being followed to manage and save the lives of the patients. There is a need for pharmacological alternatives to combat this deadly virus and its complications. Based on the previous experiences with similar coronavirus management and present preliminary data from uncontrolled studies, drugs like chloroquine, hydroxychloroquine, remdesivir, lopinavir/ritonavir, and favipiravir have been recommended by the researchers to manage COVID-19. This review had assessed the potential mechanisms, safety profile, availability and cost of these drugs. This review concludes that the drugs mentioned above are having different properties and act differently in combating the COVID-19 viruses. Instead of single drug, combination of antivirals with different mechanism of action may be more effective and at the same time their adverse events should not be underestimated.

negative: COVID-19: A promising cure for the global panic Abstract The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

negative: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.

negative: Big pharma’s quiet effort to find new coronavirus antivirals The early weeks of the coronavirus pandemic were a scramble as infectious disease experts looked for anything in the medicine cabinet that might work to treat COVID-19 Clinicians tried drugs designed for other viruses—HIV, Ebola virus, influenza viruses—hoping that the proteins they target would be similar enough to those in this virus, SARS-CoV-2 Those efforts get you only so far Viruses have subtle differences in their machinery, not to mention the way they wreak havoc on the body Even when a drug offers modest benefits, it might not be suitable for widespread use For example, Gilead Sciences’ antiviral remdesivir, originally developed for Ebola, appears to help some people with COVID-19 recover faster But it is also an intravenous drug and so can’t be used to prevent people from getting sick The medicine chest needs more options, ideally ones tailor made for this coronavirus In the past 6 weeks, big pharma

negative: Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation Summary Objectives Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. However, limited data was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 patients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan. 8 to Feb. 10, 2020. Results All 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had progressive lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progressive neutrophilia (from 4.5 to 18.28 × 109 cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus. Conclusions Findings from this small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.

negative: Mitigating the risks of surgery during the COVID-19 pandemic

negative: Managing Cutaneous Immune-Mediated Diseases During the COVID-19 Pandemic Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread rapidly worldwide and has been shown to have a wide spectrum of severity. COVID-19 has become a public health emergency of relevant international concern, and it was declared a pandemic by the World Health Organization on 11 March, 2020. SARS-CoV-2 infection in severe cases involves the host response as an important contributor to the disease process and tissue damage, mainly due to dysregulated and excessive innate immune responses. The primary immune response leads to viral clearance in the majority of cases. However, in a subgroup of patients, the secondary immune response may be exaggerated, leading to inflammatory-induced lung injury and other complications including pneumonitis, acute respiratory distress syndrome, respiratory failure, shock, organ failure, and potentially death. Several cutaneous immune-mediated diseases, including psoriasis, atopic dermatitis, and hidradenitis suppurativa, are therapeutically managed with biologic and non-biologic immunosuppressive and immunomodulatory drugs. The outbreak of COVID-19 affects the management of these chronic conditions, not only for those who are already receiving treatment but also for those who are about to start a new treatment to control their disease. In this article, the management of cutaneous immune-mediated diseases during the COVID-19 pandemic is discussed.

negative: COVID-19 in Neonates and Infants: Progression and Recovery. Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.

negative: A case report of neonatal COVID-19 infection in China In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread in many countries. Pregnant women are susceptible population of COVID-19 which are more likely to have complications and even progresse to severe illness. We report a case of neonatal COVID-19 infection in China with pharyngeal swabs tested positive by rRT-PCR assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

negative: The epidemiological and clinical features of COVID-19 and lessons from this global infectious public health event Abstract Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.

negative: Chloroquine, hydroxychloroquine, and COVID-19: systematic review and narrative synthesis of efficacy and safety Background: The COVID-19 pandemic has required clinicians to urgently identify new treatment options or the repurposing of existing drugs. Several drugs are now being repurposed with the aim of identifying if these drugs provide some level of disease resolution. Of particular interest are chloroquine (CQ) and hydroxychloroquine (HCQ), first developed as an antimalarial therapy. There is increasing concern with regards to the efficacy and safety of these agents. The aims of this review are to systematically identify and collate studies describing the use of CQ and HCQ in human clinical trials and provide a detailed synthesis of evidence of its efficacy and safety. Methods and Findings: Searches for (COVID AND chloroquine [title/abstract] AND outcomes[full text]) and two (COVID AND hydroxychloroquine[title/abstract] AND outcomes[full text]) yielded 272 unique articles. Unique articles were manually checked for inclusion and exclusion criteria and also subjected to a quality appraisal assessment. A total of 19 articles were included in the systematic review. Seventy-five percent of observational studies employing an endpoint specific to efficacy recorded no significant difference in the attainment of outcomes, between COVID-19 patients given a range of CQ and/or HCQ doses, and the control groups. All clinical trials and 82% of observational studies examining an indicator unique to drug safety discovered a higher probability of adverse events in those treated patients suspected of, and diagnosed with, COVID-19. Seventy-five percent of the total papers focusing on cardiac side-effects found a greater incidence among patients administered a wide range of CQ and/or HCQ doses, with QTc prolongation the most common finding, in addition to its consequences of VT and cardiac arrest. Of the total studies using mortality rate as an end-point, 60% reported no significant change in the risk of death, while 30% showed an elevation, and 10% a depression, in treated relative to control patients. Conclusion: The strongest available evidence suggests that, relative to standard in-hospital management of symptoms, the use of CQ and HCQ to treat hospitalised COVID-19 patients has likely been unsafe. At the very least, the poor quality of data failing to find any significant changes in the risk of VT should preclude definitive judgment on drug safety until the completion of high-quality randomised clinical trials.

negative: Data-Based Analysis, Modelling and Forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infected-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R0), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R0 as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ~4.6, while the one computed under the second scenario was found to be ~3.2. Thus, based on the SIRD simulations, the estimated average value of R0 was found to be ~2.6 based on confirmed cases and ~2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around 0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

negative: Estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: A simulation model using multivariate regression analysis Abstract Introduction and aims: To prevent the spread of coronavirus disease (COVID19) total lockdown is in place in India from March 24, 2020 for 21 days. In this study, we aim to assess the impact of the duration of the lockdown on glycaemic control and diabetes-related complications. Materials and methods A systematic search was conducted using Cochrane library. A simulation model was created using glycemic data from previous disasters (taken as similar in impact to current lockdown) taking baseline HBA1c and diabetes-related complications data from India-specific database. A multivariate regression analysis was conducted to analyse the relationship between the duration of lockdown and glycaemic targets & diabetes-related complications. Results The predictive model was extremely robust (R2 = 0.99) and predicted outcomes for period of lockdown up to 90 days. The predicted increment in HBA1c from baseline at the end of 30 days and 45 days lockdown was projected as 2.26% & 3.68% respectively. Similarly, the annual predicted percentage increase in complication rates at the end of 30-day lockdown was 2.8% for non-proliferative diabetic retinopathy, 2.9% for proliferative diabetic retinopathy, 1.5% for retinal photocoagulation, 9.3% for microalbuminuria, 14.2% for proteinuria, 2.9% for peripheral neuropathy, 10.5% for lower extremity amputation, 0.9% for myocardial infarction, 0.5% for stroke and 0.5% for infections. Conclusion The duration of lockdown is directly proportional to the worsening of glycaemic control and diabetes-related complications. Such increase in diabetes-related complications will put additional load on overburdened healthcare system, and also increase COVID19 infections in patients with such uncontrolled glycemia.

negative: Ademhaling Dyspneu is een subjectieve sensatie van inefficiënte ventilatie. Het betreft een van de meest voorkomende klachten waarmee patiënten zich op een SEH melden. De opname-indicaties zijn zeer divers. De behandeling is vooral gericht op onderliggende pathofysiologische mechanismen. Tracheobronchitis is een van de meest gestelde diagnoses; verder worden toegelicht: pneumonie, pneumothorax, longembolie, asthma bronchiale, ARDS, longoedeem, pleura-effusie en hemoptoë. Een patiënt met een acute bovensteluchtwegobstructie krijgt, zolang op gespecialiseerde hulp wordt gewacht, een zo hoog mogelijke concentratie zuurstof toegediend en er moet een noodtracheostomieset klaarstaan. Met niet-invasieve monitoring kan men de ingestelde behandeling evalueren; voor diagnosticering blijven de anamnese en het lichamelijk onderzoek van belang. Indien onverwacht een moeilijke intubatie vereist is, moeten alternatieve plannen beschikbaar zijn. Er kan een reanimatiesituatie ontstaan waarbij artsen én verpleegkundigen gerechtigd zijn alle benodigde maatregelen te nemen. Idealiter beschikt elke SEH over een algoritme/protocol dat men volgt bij patiënten met een ‘moeilijke luchtweg’.

negative: COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome. This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.

negative: Why tocilizumab could be an effective treatment for severe COVID-19? A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.

negative: Lung biopsy cells transcriptional landscape from COVID-19 patient stratified lung injury in SARS-CoV-2 infection through impaired pulmonary surfactant metabolism Clinical management of COVID-19 is still complicated due to the lack of therapeutic interventions to reduce the breathing problems, respiratory complications and acute lung injury – which are the major complications of most of the mild to critically affected patients and the molecular mechanisms behind these clinical features are still largely unknown. In this study, we have used the RNA-seq gene expression pattern in the COVID-19 affected lung biopsy cells and compared it with the effects observed in typical cell lines infected with SARS-CoV-2 and SARS-CoV. We performed functional overrepresentation analyses using these differentially expressed genes to signify the processes/pathways which could be deregulated during SARS-CoV-2 infection resulting in the symptomatic impairments observed in COVID-19. Our results showed that the significantly altered processes include inflammatory responses, antiviral cytokine signaling, interferon responses, and interleukin signaling etc. along with downmodulated processes related to lung’s functionality like-responses to hypoxia, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism. We also found that the viral protein interacting host’s proteins involved in similar pathways like: respiratory failure, lung diseases, asthma, and hypoxia responses etc., suggesting viral proteins might be deregulating the processes related to acute lung injury/breathing complications in COVID-19 patients. Protein-protein interaction networks of these processes and map of gene expression of deregulated genes revealed that several viral proteins can directly or indirectly modulate the host genes/proteins of those lung related processes along with several host transcription factors and miRNAs. Surfactant proteins and their regulators SPD, SPC, TTF1 etc. which maintains the stability of the pulmonary tissue are found to be downregulated through viral NSP5, NSP12 that could lead to deficient gaseous exchange by the surface films. Mitochondrial dysfunction owing to the aberration of NDUFA10, NDUFAF5, SAMM50 etc. by NSP12; abnormal thrombosis in lungs through atypical PLAT, EGR1 functions by viral ORF8, NSP12; dulled hypoxia responses due to unusual shift in HIF-1 downstream signaling might be the causative elements behind the acute lung injury in COVID-19 patients. Our study put forward a distinct mechanism of probable virus induced lung damage apart from cytokine storm and advocate the need of further research for alternate therapy in this direction.

negative: Shedding Light on Dysphagia Associated With COVID-19: The What and Why The most common symptom of COVID-19 in critically ill patients is ARDS (acute respiratory distress syndrome), with many patients requiring invasive or noninvasive respiratory support in the intensive care unit. Oropharyngeal dysphagia may be a consequence of the respiratory-swallowing incoordination common in ARDS or may occur following the respiratory support interventions. In this commentary, we highlight the risk and complications of oropharyngeal dysphagia in patients with COVID-19 and urge medical and rehabilitation professionals to consider dysphagia a prognostic complication, provide appropriate referrals, and initiate early interventions as appropriate.

negative: Guidance for the care of neuromuscular patients during the COVID-19 pandemic outbreak from the French Rare Health Care for Neuromuscular Diseases Network Abstract In France, the epidemic phase of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in February 2020 and resulted in the implementation of emergency measures and a degradation in the organization of neuromuscular reference centers. In this special context, the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) has established guidance in an attempt to homogenize the management of neuromuscular (NM) patients within the French territory. Hospitalization should be reserved for emergencies, the conduct of treatments that cannot be postponed, check-ups for which the diagnostic delay may result in a loss of survival chance, and cardiorespiratory assessments for which the delay could be detrimental to the patient. A national strategy was adopted during a period of 1 to 2 months concerning treatments usually administered in hospitalization. NM patients treated with steroid/ immunosuppressants for a dysimmune pathology should continue all of their treatments in the absence of any manifestations suggestive of COVID-19. A frequently asked questions (FAQ) sheet has been compiled and updated on the FILNEMUS website. Various support systems for self-rehabilitation and guided exercises have been also provided on the website. In the context of NM diseases, particular attention must be paid to two experimental COVID-19 treatments, hydroxycholoroquine and azithromycin: risk of exacerbation of myasthenia gravis and QT prolongation in patients with pre-existing cardiac involvement. The unfavorable emergency context related to COVID-19 may specially affect the potential for intensive care admission (ICU) for people with NMD. In order to preserve the fairest medical decision, a multidisciplinary working group has listed the neuromuscular diseases with a good prognosis, usually eligible for resuscitation admission in ICU and, for other NM conditions, the positive criteria suggesting a good prognosis. Adaptation of the use of noninvasive ventilation (NIV) make it possible to limit nebulization and continue using NIV in ventilator-dependent patients.

negative: Differential effect of cholesterol on type I and II feline coronavirus infection Feline infectious peritonitis (FIP) is a fatal disease of domestic and wild felidae that is caused by feline coronavirus (FCoV). FCoV has been classified into types I and II. Since type I FCoV infection is dominant in the field, it is necessary to develop antiviral agents and vaccines against type I FCoV infection. However, few studies have been conducted on type I FCoV. Here, we compare the effects of cholesterol on types I and II FCoV infections. When cells were treated methyl-β-cyclodextrin (MβCD) and inoculated with type I FCoV, the infection rate decreased significantly, and the addition of exogenous cholesterol to MβCD-treated cells resulted in the recovery of the infectivity of type I FCoV. Furthermore, exogenous cholesterol increased the infectivity of type I FCoV. In contrast, the addition of MβCD and exogenous cholesterol had little effect on the efficiency of type II FCoV infection. These results strongly suggest that the dependence of infection by types I and II FCoV on cholesterol differs.

negative: COVID-19 infection in kidney transplant recipients By 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. It is unknown if immunocompromised hosts are at higher risk of more severe systemic disease. Therefore, we report on seven cases of COVID-19 in kidney transplant recipients (median age 54 (range 45-69), three females, from a cohort of 2082 managed transplant follow-up patients) over a six-week period in three south London hospitals. Two of 32 patients presented within three months of transplantation. Overall, two were managed on an out-patient basis, but the remaining five required hospital admission, four in intensive care units. All patients displayed respiratory symptoms and fever. Other common clinical features included hypoxia, chest crepitation, lymphopenia and high C-reactive protein. Very high D dimer, ferritin and troponin levels occurred in severe cases and likely prognostic. Immunosuppression was modified in six of seven patients. Three patients with severe disease were diabetic. During a three week follow up one patient recovered, and one patient died. Thus, our findings suggest COVID-19 infection in kidney transplant patients may be severe, requiring intensive care admission. The symptoms are predominantly respiratory and associated with fever. Most patients had their immunosuppression reduced and were treated with supportive therapy.

negative: A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19 Background: Although a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. Methods: A review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms “2019-nCoV”, “COVID-19”, “SARS-CoV-2”, “Hcov-19”, “new coronavirus”, “novel coronavirus”. We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents. Findings: Out of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). Interpretation: Numerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking. Funding: None

negative: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.

negative: Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression The current outbreak of Coronavirus Disease 2019 (COVID‐19) has raised great concern worldwide, but its impact on transplant recipients is unknown. We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID‐19 pneumonia. This is a 52‐year‐old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non‐transplanted COVID‐19 patients. Following a treatment regimen consisting of reduced immunosuppressant use and low dose methylprednisolone‐based therapy, the COVID‐19 pneumonia in this long‐term immunosuppressive patient was successfully recovered. This effectively treated case has reference value for the future treatment of other transplant patients with COVID‐19 pneumonia.

negative: Prediction of the number of deaths in India due to SARS-CoV-2 at 5–6 weeks Abstract Introduction and Aims: No valid treatment or preventative strategy has evolved till date to counter the SARS CoV 2 (Novel Coronavirus) epidemic that originated in China in late 2019 and have since wrought havoc on millions across the world with illness, socioeconomic recession and death. This analysis was aimed at tracing a trend related to death counts expected at the 5th and 6th week of the COVID-19 in India. Material and methods Validated database was used to procure global and Indian data related to coronavirus and related outcomes. Multiple regression and linear regression analyses were used interchangeably. Since the week 6 death count data was not correlated significantly with any of the chosen inputs, an auto-regression technique was employed to improve the predictive ability of the regression model. Results A linear regression analysis predicted average week 5 death count to be 211 with a 95% CI: 1.31–2.60). Similarly, week 6 death count, in spite of a strong correlation with input variables, did not pass the test of statistical significance. Using auto-regression technique and using week 5 death count as input the linear regression model predicted week 6 death count in India to be 467, while keeping at the back of our mind the risk of over-estimation by most of the risk-based models. Conclusion According to our analysis, if situation continue in present state; projected death rate (n) is 211 and467 at the end of the 5th and 6th week from now, respectively.

negative: Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019

negative: Impact of COVID-19 related healthcare crisis on treatments for patients with lysosomal storage disorders, the first Italian experience Abstract The direct and indirect effects of Coronavirus Disease-19 (COVID-19) pandemic, on Italian patients with lysosomal storage disorders receiving therapy, were analyzed by a phone questionnaire. No proved COVID-19 emerged among 102 interviewed. No problems were reported by patients receiving oral treatments. Forty-nine% of patients receiving enzyme replacement therapy in hospitals experienced disruptions, versus 6% of those home-treated. The main reasons of missed infusions were fear of infection (62.9%) and re-organization of the infusion centers (37%).

negative: Mathematical model of infection kinetics and its analysis for COVID-19, SARS and MERS Abstract The purpose of this paper is to reveal the spread rules of the three pneumonia: COVID-19, SARS and MERS. We compare the new spread characteristics of COVID-19 with those of SARS and MERS. By considering the growth rate and inhibition constant of infectious diseases, their propagation growth model is established. The parameters of the three coronavirus transmission growth models are obtained by nonlinear fitting. Parametric analysis shows that the growth rate of COVID-19 is about twice that of the SARS and MERS, and the COVID-19 doubling cycle is two to three days, suggesting that the number of COVID-19 patients would double in two to three days without human intervention. The infection inhibition constant in Hubei is two orders of magnitude lower than in other regions, which reasonably explains the situation of the COVID-19 outbreak in Hubei.

negative: COVID-19: what has been learned and to be learned about the novel coronavirus disease The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.

negative: Return of the Coronavirus: 2019-nCoV The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.

negative: Rehospitalization of a Recovered Coronavirus Disease 19 (COVID-19) Child With Positive Nucleic Acid Detection Since December 2019, novel coronavirus-infected pneumonia (coronavirus disease 19) occurred in Wuhan and rapidly spread throughout China and beyond. During this period, increasing of reports found that several recovered patients from different hospitals showed positive results of nucleic acid test again soon after discharge. However, little attention has been paid to recovered children. Herein, we reported a case of 8-year-old recovered child, who was rehospitalized again because of unexplained fever.

negative: Social and administrative issues related to the COVID-19 pandemic in Pakistan: better late than never The study critically reviewed Pakistan’s provincial updates of coronavirus disease 2019 (COVID-19) and discussed the current challenges faced by the government in a given context. The coronavirus-associated death tolls have been increasing rapidly in a country. The provincial status of confirmed cases of coronavirus is higher in Punjab, followed by the Sindh, Khyber Pakhtunkhwa (KPK), and Balochistan. The case fatality ratio shows that KPK has a higher ratio, i.e., 5.11%, followed by the Punjab, i.e., 1.82%; Sindh, i.e., 1.80%; Balochistan, i.e., 1.28%; Gilgit-Baltistan, i.e., 0.71%; and Federal territory, i.e., 0.66%. The country has a less testing capacity to identify more suspected coronavirus patients. The study calculated that if we increase five times our testing capacity from the current date, the total registered cases will be reached to 137,370 and death tolls will increase up to 3090. It is highly needed to increase testing capacity across Pakistan in order to minimize the outbreak of coronavirus. The provincial government should follow the Federal Government instructions to contain coronavirus by increasing testing capacities, tracing suspected patients, smart lockdowns, emergency relief to the poor, and vigilant monitoring system.

negative: A Structured Approach for Safely Reintroducing Bariatric Surgery in a COVID-19 Environment Due to the profound effect of novel coronavirus disease 2019 (COVID-19) on healthcare systems, surgical programs across the country have paused surgical operations and have been utilizing virtual visits to help maintain public safety. For those who treat obesity, the importance of bariatric surgery has never been more clear. Emerging studies continue to identify obesity and several other obesity-related comorbid conditions as major risk factors for a more severe COVID-19 disease course. However, this also suggests that patients seeking bariatric surgery are inherently at risk of suffering severe complications if they were to contract COVID-19 in the perioperative period. The aim of this protocol is to utilize careful analysis of existing risk stratification for bariatric patients, novel COVID-19-related data, and consensus opinion from multiple academic bariatric centers within our organization to help guide the reanimation of our programs when appropriate and to use this template to prospectively study this risk-stratified population in real time. The core principles of this protocol can be applied to any surgical specialty.

negative: Safety and efficacy of perioperative benzodiazepine administration: study protocol for a systematic review and meta-analysis. INTRODUCTION Perioperative benzodiazepines are used because of their anxiolytic, sedative and amnestic effects. Evidence has demonstrated an association of benzodiazepines with adverse neuropsychiatric effects. Nonetheless, because of their potential benefits, perioperative benzodiazepines continue to be used routinely. We seek to evaluate the body of evidence of the risks and benefits of benzodiazepine use during the perioperative period. METHODS AND ANALYSIS We will search Cochrane CENTRAL, MEDLINE, EMBASE, PsychINFO, CINAHL and Web of Science from inception to March 2019 for randomised controlled trials (RCTs) and observational studies evaluating the administration of benzodiazepine medications as compared with all other medications (or nothing) in patients undergoing cardiac and non-cardiac surgery. We will exclude studies assessing the use of benzodiazepines for procedural sedation or day surgery. We will examine the impact of giving these medications before, during and after surgery. Outcomes of interest include the incidence of delirium, duration of delirium, postprocedure cognitive change, the incidence of intraoperative awareness, patient satisfaction/quality of life/quality of recovery, length-of-stay (LOS) in the intensive care unit (ICU), hospital LOS and in-hospital mortality.Reviewers will screen references and assess eligibility using predefined criteria independently and in duplicate. Two reviewers will independently collect data using prepiloted forms. We will present results separately for RCTs and observational studies. We will pool data using a random effect model and present results as relative risk with 95% CIs for dichotomous outcomes and mean difference with 95% CI for continuous outcomes. We will pool adjusted ORs for observational studies. We will assess risk of bias for individual studies using the Cochrane Collaboration tool for RCTs. For observational studies, we will use tools designed by the Clinical Advances through Research and Information Translation group. Quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION This systematic review involves no patient contact and no interaction with healthcare providers or systems. As such, we did not seek ethics board approval. We will disseminate the findings of our systematic review through the presentation at peer-reviewed conferences and by seeking publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019128144.

negative: Validating a Widely Implemented Deterioration Index Model Among Hospitalized COVID-19 Patients Introduction: The coronavirus disease 2019 (COVID-19) pandemic is straining the capacity of U.S. healthcare systems. Accurately identifying subgroups of hospitalized COVID-19 patients at high- and low-risk for complications would assist in directing resources. Objective: To validate the Epic Deterioration Index (EDI), a predictive model implemented in over 100 U.S. hospitals that has been recently promoted for use in COVID-19 patients. Methods: We studied adult patients admitted with COVID-19 to non-ICU level care at a large academic medical center from March 9 through April 7, 2020. We used the EDI, calculated at 15-minute intervals, to predict a composite adverse outcome of ICU-level care, mechanical ventilation, or death during the hospitalization. In a subset of patients hospitalized for at least 48 hours, we also evaluated the ability of the EDI (range 0-100) to identify patients at low risk of experiencing this composite outcome during their remaining hospitalization. We evaluated model discrimination and calibration using both raw EDI scores and their slopes. Results: Among 174 COVID-19 patients meeting inclusion criteria, 61 (35%) experienced the composite outcome. Area under the receiver-operating-characteristic curve (AUC) of the EDI was 0.76 (95% CI 0.68-0.84). Patients who met or exceeded an EDI of 64.8 made up 17% of the study cohort and had an 80% probability of experiencing the outcome during their hospitalization with a median lead time of 28 hours from when the threshold was first exceeded to the outcome. Employing the EDI slope lowered the AUCs to 0.68 (95% CI 0.60-0.77) and 0.67 (95% CI 0.59-0.75) for slopes calculated over 4 and 8 hours, respectively. In a subset of 109 patients hospitalized for at least 48 hours and who had not experienced the composite outcome, 14 (13%) patients who never exceeded an EDI of 37.9 had a 93% probability of not experiencing the outcome throughout the rest of their hospitalization, suggesting low risk. Conclusion: In this validation study, we found the EDI identifies small subsets of high- and low-risk patients with fair discrimination. These findings highlight the need for hospitals to carefully evaluate prediction models before widespread operational use among COVID-19 patients.

negative: What triggers online help-seeking retransmission during the COVID-19 period? Empirical evidence from Chinese social media The past eight months witnessed COVID-19's fast-spreading at the global level. Limited by medical resources shortage and uneven facilities distribution, online help-seeking becomes an essential approach to cope with public health emergencies for many ordinaries. This study explored the driving forces behind the retransmission of online help-seeking posts. We built an analytical framework that emphasized content characteristics, including information completeness, proximity, support seeking type, disease severity, and emotion. Adopting the framework, a quantitative content analysis was conducted with a probability sample of 727 posts. The results illustrate the importance of individual information completeness, high proximity, instrumental support seeking. This study also reveals the severity principle and the power of anger in the dissemination of help-seeking messages. As one of the first online help-seeking diffusion analyses in the COVID-19 period, the theoretical and practical implications of this study are further discussed.

negative: Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19 Abstract Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people, meaning people with close contact with positive tested patients, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at does matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people.

negative: Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

negative: An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov) The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.

negative: COVID-19 in Kenya COVID-19 meaning Coronavirus disease which is severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) discovered in the year December 2019 at Wuhan in China after an outbreak an infectious disease causing respiratory illness-pneumonia. SARS-CoV-2 was previously known as 2019 novel Coronavirus disease or 2019-nCov. Kenya has 122 positive cases of COVID-19 as at 4thApril 2020, four deaths and three recoveries as reported by the Government of Kenya.

negative: Ethnicity, comorbidity, socioeconomic status, and their associations with COVID-19 infection in England: a cohort analysis of UK Biobank data Objectives: Recent data suggest higher COVID-19 rates and severity in Black, Asian, and minority ethnic (BAME) communities. The mechanisms underlying such associations remain unclear. We aimed to study the association between ethnicity and risk of COVID-19 infection and disentangle any correlation with socioeconomic deprivation or previous comorbidity. Design: Prospective cohort. Setting: UK Biobank linked to Hospital Episode Statistics (HES) and COVID-19 tests until 14 April 2020. Participants: UK Biobank participants from England, excluding drop-outs and deaths. Main measures: COVID-19 infection based on a positive PCR test. Ethnicity was self-reported and classified using Office of National Statistics groups. Socioeconomic status was based on index of multiple deprivation quintiles. Comorbidities were self-reported and completed from HES. Analyses: Multivariable Poisson analysis to estimate incidence rate ratios of COVID-19 infection according to ethnicity, adjusted for socioeconomic status, alcohol drinking, smoking, body mass index, age, sex, and comorbidity. Results: 415,582 participants were included, with 1,416 tested and 651 positive for COVID-19. The incidence of COVID-19 was 0.61% (95% CI: 0.46%-0.82%) in Black/Black British participants, 0.32% (0.19%-0.56%) in other ethnicities, 0.32% (0.23%-0.47%) in Asian/Asian British, 0.30% (0.11%-0.80%) in Chinese, 0.16% (0.06%-0.41%) in mixed, and 0.14% (0.13%-0.15%) in White. Compared with White participants, Black/Black British participants had an adjusted relative risk (RR) of 3.30 (2.39-4.55), Chinese participants 3.00 (1.11-8.06), Asian/Asian British participants 2.04 (1.36-3.07), other ethnicities 1.93 (1.08-3.45), and mixed ethnicities 1.07 (0.40-2.86). Socioeconomic status (adjusted RR 1.93 (1.51-2.46) for the most deprived), obesity (adjusted RR 1.04 (1.02-1.05) per kg/m2) and comorbid hypertension, chronic obstructive pulmonary disease, asthma, and specific renal diseases were also associated with increased risk of COVID-19. Conclusions: COVID-19 rates in the UK are higher in BAME communities, those living in deprived areas, obese patients, and patients with previous comorbidity. Public health strategies are needed to reduce COVID-19 infections among the most susceptible groups.

negative: Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018 BACKGROUND: Patients infected with the novel coronavirus (SARS-CoV-2) are being treated empirically with oseltamivir, but there is little evidence from randomised controlled trials to support the treatment of coronavirus infections with oseltamivir. AIM: To determine whether adding oseltamivir to usual care reduces time to recovery in symptomatic patients who have tested positive for coronavirus (not including SARS-CoV-2). DESIGN AND SETTING: Exploratory analysis of data from an open-label, pragmatic, randomised controlled trial during three influenza seasons, from 2016 to 2018, in primary care research networks, in 15 European countries. METHOD: Patients aged ≥1 year presenting to primary care with influenza-like illness (ILI), and who tested positive for coronavirus (not including SARS-CoV-2), were randomised to usual care or usual care plus oseltamivir. The primary outcome was time to recovery defined as a return to usual activities, with minor or absent fever, headache, and muscle ache. RESULTS: Coronaviruses (CoV-229E, CoV-OC43, CoV-KU1 and CoV-NL63) were identified in 308 (9%) out of 3266 randomised participants in the trial; 153 of these were allocated to usual care and 155 to usual care plus oseltamivir; the primary outcome was ascertained in 136 and 147 participants, respectively. The median time to recovery was shorter in patients randomised to oseltamivir: 4 days (interquartile range [IQR] 3-6) versus 5 days (IQR 3-8; hazard ratio 1.31; 95% confidence interval = 1.03 to 1.66; P = 0.026). CONCLUSION: Primary care patients with ILI testing positive for coronavirus (not including SARS-CoV-2) recovered sooner when oseltamivir was added to usual care compared with usual care alone. This may be of relevance to the primary care management of COVID-19.

negative: Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO Despite being mainly a respiratory virus, cardiac complications have been described These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19 The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications Received 6 April 2020 Accepted 14 April 2020 Correspondence to Antoine Fakhry AbdelMassih, MD, Pediatrics’ Department, Pediatric Cardiology unit, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 12411, Egypt, E-mail: antoine abdelmassih@kasralainy edu eg © 2020Wolters Kluwer Health Lippincott Williams Wilkins

negative: Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia. Methods: In this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients. Conclusion: Our results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.

negative: Novel Coronavirus and Related Public Health Interventions Are Negatively Impacting Mental Health Services

negative: Impact of COVID 19 lockdown on orthopaedic surgeons in India: A survey() BACKGROUND: In the fight against COVID 19, the government of India announced a 3 weeks lockdown of the entire country of 1.3 billion people on 24(th) March 2020. METHODS: One week after the lockdown was announced, we conducted an anonymous online survey of the orthopaedic surgeons in India through social media platforms to assess the impact of the lockdown during COVID 19. The survey had a total of 13 questions with (3–5) options and was designed with an aim to understand the perception and the state of mind of the Orthopaedic surgeons in the lockdown situation. RESULTS: The survey was completed by 611 orthopaedic surgeons from 140 cities in India. There were 22.5% orthopaedic surgeons who said that they were definitely stressed out, and 40.5% who said they were mildly stressed out. As the age decreased, the percentage of orthopaedic surgeons feeling “definitely stressed out” increased. Disruption of life-work balance and uncertainties regarding return to work were other strongly associated factors with the “definitely stressed out” group. CONCLUSION: The psychological impact of the lockdown during COVID 19 on orthopaedic surgeons may become a potential concern that will require addressal through open discussion. LEVEL OF EVIDENCE: diagnostic level 4.

negative: Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia Coronavirus Disease 2019 (COVID-19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After its first occurrence in Wuhan of China from December 2019, COVID-19 rapidly spread around the world. According to the World Health Organization statement on 13 March 2020, there had been over 132 500 confirmed cases globally. Nevertheless, the case reports of children are rare, which results in the lack of evidence for preventing and controlling of children's infection. Here, we report three cases of SARS-CoV-2 infected children diagnosed from 3 February to 17 February 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after the treatment, with the nucleic acid of throat swab turning negative within 14, 11, and 7 days after diagnosis, respectively. However, after been discharged, all three cases were tested SARS-CoV-2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal-oral transmission of SARS-CoV-2 infection, especially for children cases.

negative: $100M in Dislocated Worker grants available

negative: Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.

negative: Predicting optimal lockdown period with parametric approach using three-phase maturation SIRD model for COVID-19 pandemic This paper proposes a three-phase Susceptible-Infected-Recovered-Dead (SIRD) model to calculate an optimal lockdown period for some specific geographical regions that will be favorable to break not only the transmission chain but also will help country’s economy to recover and support infrastructure in a fight against COVID-19. Proposed model is novel since it additionally includes parameters i.e. silent carriers, sociability of newly infected person and unregistered died coronavirus infected people along with the infection rate, suspected rate and death rate. These parameters contribute a lot to figure out the more clear model, along with essential parameters. The model takes the testing rate of suspected people into consideration and this rate varies with respect to phase of the epidemic growth. Proposed SIRD model is divided into three phases based on the awareness and sustainability of disease. Time is divided into different periods as rate of infection and recovery fluctuates region to region. The model is tested on China data and is efficient enough to propose a model very close to their actual figures of infected people, recovered people, died and active cases. The model predicts the optimal lockdown period as 73 days for China which is very close to their actual lockdown period (77 days). Further, the model is implemented to predict the optimal lockdown period of India and Italy.

negative: Killing Two Birds with One Stone? Green Dead Ends and Ways Out of the COVID-19 Crisis The coronavirus crisis has opened up a window of opportunity for transformation. This should be used without getting off the regulatory track. Green recovery programs must not be reduced to a mere competition for green subsidies. Abandoning barriers to green investments and imposing a carbon price are equally important. Where economically sensible, green subsidies should contribute both to stabilizing the economy and mitigating climate change. Moreover, smart green recovery programs may contribute to raising revenues for the additionally necessary public expenditures.

negative: Indwelling double pigtail ureteral stent combined or not with surgery for feline ureterolithiasis: complications and outcome in 15 cases. Ureteral obstruction secondary to ureterolithiasis in cats is a challenging situation. Ureteral stenting has recently been introduced to prevent complications that often occurred after ureterotomy or other invasive surgeries. The purpose of this study is to describe the stenting technique and perioperative difficulties, as well as long-term outcome and complications with ureteral stenting in 12 cats with ureteroliths. Fifteen 2.5 Fr soft double pigtail multi-fenestrated ureteral stents were placed in an anterograde fashion under open surgical approaches and with fluoroscopic guidance in 12 cats. Nine cats received a unilateral stent and three received bilateral stents. Ureterotomy or ureteral resection and end-to-end anastomosis were performed in three and four cases, respectively. In six cats, papillotomy was performed to facilitate dilatator and stent placement. All cats recovered well from the surgical procedure, except one cat, which died during the anaesthesia recovery period. Postoperative complications included dysuria (three cases, diagnosed at 15 days, 1 month and 3 months, respectively), urinary tract infection (one case, 1 month after surgery), stent migration requiring stent replacement (one case, 19 months after surgery) and stent obstruction requiring stent removal (three cases with previously end-to-end anastomosis between 2 and 8 months after surgery). Nine cats (75%) were alive at a mean follow-up of 453 ± 194 (123-720) days. The median survival time was >415 days. Stent placement appeared to be a valuable and safe option for treating ureteral obstruction in cats. However, periodic and long-term monitoring of stents is warranted.

negative: Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance Abstract Alarming situation has been caused due to the emergence of COVID-19 infection around the world. There is an urgency of developing a therapeutic strategy in order to control the spread of COVID-19. Towards that initiative, potential drugs like hydroxychloroquine, ivermectin and azithromycin have been tested by diverse group of researchers worldwide for their potential against novel coronavirus. The present report presents together the comprehensive knowledge derived from the major researches about the above drugs altogether in context of the current health emergency around the world. Hydroxychloroquine and ivermectin were known to act by creating the acidic environment and inhibiting the importin (IMPα/β1) mediated viral import. Azithromycin was found to act similar to the hydroxychloroquine as an acidotropic lipophilic weak base. All the three categories of drugs seemed to potentially act against novel coronavirus infection. However, their efficacies need to be studied in detail individually and in combination in-vivo in order to combat COVID-19 infection.

negative: Coronavirus infections of man associated with diseases other than the common cold About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1 % of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody litres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups.

negative: Coronavirus-like particles in nonhuman primate feces Coronavirus-like particles were detected by electron microscopy in normal and diarrhea stool specimens from baboons, chimpanzees, macaques, and marmosets. There was a high prevalence of particles in both normal and diarrhea stools of older animals, whereas stools from nonweaned animals rarely contained these coronavirus-like particles.

negative: Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson-Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev. 2019, 119, 9478; Wang, Curr. Comput.-Aided Drug Des. 2006, 2, 287; Wang; ; Hou J. Chem. Inf. Model., 2012, 52, 1199). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.8 kcal/mol) is not nearly as low as that of the neutral form (-7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.9 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.

negative: Molecular basis of COVID-19 relationships in different species: a one health perspective Abstract Outside the Hubei province, China, the mild form of infection and the progressive recover of the COVID-19 patients suggest the intervention of “unconventional” biological mechanisms worthy of attention. Based on the high-homology between the Spike protein epitopes of taxonomically-related coronaviruses, we hypothesized that past contact with infected dogs shield humans against the circulating SARS-CoV-2. Elseways, the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province. Nevertheless, further experimental studies are desired for a confidential evaluation of the postulated hypotheses.

negative: New understanding of the damage of SARS-CoV-2 infection outside the respiratory system Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

negative: What is the best drug to treat COVID-19? The need for randomized controlled trials The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest public health challenge to the biomedical community of the last century Despite multiple public health measures, 1-3 there remains an urgent need for pharmacologic therapies to treat infected patients and minimize mortality, decrease pressures on intensive care units and health systems and optimally they should decrease subsequent transmission At the time of writing, there are no licensed drugs to treat COVID-19 and a search on clinicaltrials gov using ‘COVID-19’ as the input term, yielded 657 studies Drug-based interventions currently fall into categories including off label use which includes repurposed drugs, 4,5 and newer entities but both categories should be given in the context of clinical trials In Wuhan, China, then the epicentre of the pandemic, Cao et al under heroic circumstances, conducted a randomized, controlled, open-label trial involving 199 hospitalized patients with confirmed SARS-CoV-2 infection including as an entry criteria oxygen saturation (SaO2) of 94% or less on air (ChiCTR2000029308) Patients were randomly assigned 1:1 to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice daily for 14 days, or standard care alone The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first 6 Even though their study showed no benefits with lopinavir–ritonavir treatment beyond standard care, this is exactly the sort of study that best informs our treatment options Following this, we were surprised to see the New England Journal of Medicine publishing a single arm study on 61 patients who received at least one dose of remdesevir, again with similar entry criteria of SaO2 <94% on air 7 Unlike the randomised trial by Cao et al , there was no accompanying editorial, but there was a subsequent an open letter discussing remdesevir studies from the CEO and Chairman of Gilead (https://www gilead com/stories/articles/an-open-letter-from-our-chairman-and-ceo) One presumes that the patients in the remdesevir single arm study, and several included in an earlier Lancet paper, 8 were recruited in perhaps easier conditions than those in Wuhan earlier this year Randomised trials are designed to precisely answer questions regarding toxicity and efficacy beyond standard of care and in the absence of an effective therapy it remains entirely reasonable and ethical at this point to perform a trial versus placebo They are much more informative than single arm studies which result in claims, perhaps borne from hope and/or desperation, that drugs work, 9 and such claims include those from physicians stating very high cure rates Clearly, recruiting patients recently diagnosed will have ‘cure rates’ usually in the high 90s%, unless one focuses on recruiting hospitalised patients and/or the elderly, frail, those with co-morbidities or a high body mass index, to name a few examples A well-known French microbiologist on social media has promoted the use of chloroquine to treat or prevent COVID-19 The FDA has approved it, although at the time of writing they haven’t explained the rationale behind the approval, and as a consequence patients, institutions and the worried public have demanded immediate chloroquine for all The resulting rush on chloroquine has led to severe shortages of the drug, and patients taking regular chloroquine or hydroxychloroquine for lupus or other systemic diseases had to stop their treatment due to a lack of supply This drug has well known often serious toxicities;10 we note one small study was stopped due to potential cardiac complications (https://www nytimes com/2020/04/12/health/chloroquine-coronavirus-trump html) and we suggest it should only be taken in the context of a randomised or other clinical study This is not to suggest single arm studies are not helpful: they inform subsequent trials includi g dosage, duration and appropriate endpoints For example, we have observed11 that use of baricitinib for 10 days is associated with viral rebound in nasopharyngeal swabs in rapidly recovered and discharged patients, and thus have recommended longer use in the large randomised studies in which it is included, and we suggest again that comparisons between different therapies or placebo are likely to yield more informative results than randomised studies comparing 10 days of intravenous remdesevir with 5 days (https://benevolent ai/news/potential-treatment-for-covid-19-identified-by-benevolentai-usingartificial-intelligence-enters-clinical-testing And https://investor lilly com/news-releases/news-release-details/lilly-begins-clinical-testingtherapies-covid-19) With this in mind, we thoroughly congratulate the authors from Guangzhou, China, who successfully randomised 86 individuals with mild-to-moderate COVID-19 in a 2:2:1 design, to either lopinavir/ritonavir, arbidol (a broad spectrum viral infusion inhibitor12) or placebo (NCT04252885) Because they included only mild-to-moderate patients, the pre-defined primary endpoint was the conversion at day 21 of positive-to-negative PCR tests for SARSCoV-2 from nasopharyngeal swabs The real time reverse-transcriptase PCR (RT-PCR) method used was indeed appropriate as it was performed simultaneously on two target genes, ORF1ab and N genes, and positive and negative controls were used at each batch Negative conversion required 2 separate real time RT-PCR tests separated by 24 hours, and the entry criteria for the definition of mild-to-moderate including the absence of pneumonia are entirely appropriate Baseline criteria between the 3 groups were well-matched (a criticism of one of the hydroxychloroquine randomised studies is this was not the case13) and follow up was appropriate Their data helpfully shows there was no difference between any of the groups in the primary endpoint In the continuing search for safe and effective new therapies to treat patients with COVID-19, we require well-conducted ethical studies including prospective, randomised, placebocontrolled clinical studies such as this Although many drugs have predicted in vitro activity against the virus, the proposal that such drugs might provide more benefit than harm is not appropriate with no evidence base supporting efficacy in any patients infected with SARSCoV-2 A preprint reporting results from a randomised trial of the anti-viral favipravir versus arbidol in 240 adults has shown no difference in clinical recovery at 7 days, but cough and pyrexia were improved on favipravir 14 These authors and Li et al should be applauded for their efforts to add a useful randomised trial to the literature, albeit one that is negative It is critical to publish such studies International multicentre trials, such as Discovery (NCT04315948) and Solidarity (EudraCT Number 2020-000982-18), will randomise patients with COVID-19 to receive different drugs in adaptive study designs Such initiatives will provide the best and most relevant data to guide management of patients with COVID-19 Whether antiviral, immunomodulatory or antimalarial drugs could be effective in changing the disease course in patients with either mild or severe COVID-19 remains unknown When patients take these off-label and recover it is not known whether the drug was helpful in the disease course without randomisation Similarly, when patients deteriorate, we do not know if they should be continued or considered clinically ineffective and stopped Assessing viral loads by PCR on nasopharyngeal swabs as performed in the trial here, will help clarify the roles of these medicines going forwards

negative: A retrospective study of the clinical characteristics of COVID-19 infection in 26 children Background: The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.

negative: Clinical analysis of ten pregnant women with COVID-19 in Wuhan, China: A retrospective study Abstract Background COVID-19 is spreading globally. This study aims to evaluate the clinical characteristics and outcomes of pregnant women confirmed with COVID-19 to provide reference for clinical work. Methods The clinical features and outcomes of 10 pregnant women confirmed with COVID-19 at Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, a tertiary- care teaching hospital in Hubei province, Wuhan, China from January 23 to February 23, 2020 were retrospectively analyzed. Results All the 10 observed pregnant women including 9 singletons and 1 twin were native people in Wuhan. All of them were diagnosed mild COVID-19, and none one of the patients developed severe COVID-19 or died. Among the 10 patients, two patients underwent vaginal delivery, two patients underwent intrapartum cesarean section, and the remaining six patients underwent elective cesarean section. All of 10 patients showed lung abnormalities by pulmonary CT images after delivery. Their eleven newborns were recorded and no neonatal asphyxia was observed. Conclusions Pulmonary CT screening on admission may be necessary to reduce the risk of nosocomial transmission of COVID-19 during the outbreak period. And COVID-19 is not an indication of cesarean section.

negative: Respiratory Viruses The respiratory viruses as a group are the most common cause of an acute infectious illness in developed societies. The immunocompromised state of many cancer patients constitutes the basis for the frequent failure of the host to promote a normal and rapid recovery from an acute respiratory viral infection and results in a more severe and prolonged infection that causes significant morbidity and mortality in these patients. Those respiratory viruses that are most prevalent and most prone to produce lower respiratory illnesses and pneumonia in healthy hosts, RSV, influenza viruses, and parainfluenza viruses, are those most likely to cause severe illness and pneumonia leading to hospitalization in immunocompromised persons. However, viruses less prone to produce a lower respiratory illness but that are highly prevalent, such as rhinoviruses, may frequently be associated with severe illness. The limited availability of antivirals and vaccines for the acute respiratory viruses means that these infections will continue to be important for many years and dictate a need for utilizing infection control procedures as much as possible, particularly in hospitals and institutions, so as to minimize spread. Efforts to develop specific vaccines are important as their use could prevent as well as reduce exposure of cancer patients to these viruses. Development of specific antivirals is important for use in immunocompromised patients as normal recovery mechanisms may be seriously impaired.

negative: Late Noninfectious Pulmonary Complications in Hematopoietic Stem Cell Transplantation Hematopoietic stem cell transplantation (HSCT) is an established therapeutic modality for a number of malignant and nonmalignant conditions. Pulmonary complications following HSCT are associated with increased mortality and morbidity. These complications may be classified into infectious versus noninfectious, and early versus late based on the time of occurrence post-transplant. Thus, exclusion of infectious etiologies is the first step in the diagnoses of pulmonary complications. Late onset noninfectious pulmonary complications typically occur 3 months post-transplant. Bronchiolitis obliterans is the major contributor to late-onset pulmonary complications, and its clinical presentation, pathogenesis, and current therapeutic approaches are discussed. Idiopathic pneumonia syndrome is another important complication which usually occurs early, although its onset may be delayed. Organizing pneumonia is important to recognize due to its responsiveness to corticosteroids. Other late onset noninfectious pulmonary complications discussed here include pulmonary venoocclusive disease, pulmonary cytolytic thrombi, pleuroparenchymal fibroelastosis, thoracic air leak syndrome, and posttransplant lymphoproliferative disorders.

negative: Food security and Canada's agricultural system challenged by COVID‐19 The effect of COVID‐19 on Canadian food security is examined from two different perspectives. COVID‐19 creates a unique “income shock” that is expected to increase the prevalence of household food insecurity. This food insecurity can be measured by utilizing the Canadian Community Health Survey (CCHS). More fundamentally, COVID‐19 heightens household concern about the capacity of the Canadian food system to ensure food availability. Despite surges in demand and supply chain disruptions, we currently do not observe broad, rapid appreciation in food prices. This suggests that there is an adequate supply of food for the near term. There is less certainty over intermediate and longer time periods because so many factors are in flux, particularly the rate of increases in sicknesses and deaths across the country and globally. Data on these health factors and elements of the food supply chain are needed to predict beyond a short time frame. In this regard, we discuss three ongoing considerations—ease of capital flows, international exchange, and maintaining transportation—that will help ensure food availability in the longer run.

negative: Community Pharmacists: On the frontline of health service against COVID-19 in LMICs Abstract The COVID-19 outbreak is a global public health crisis which has affected healthcare practice across professions. In the context of this pandemic, there is a need to highlight the roles and responsibilities of pharmacists. Community pharmacists are the most accessible healthcare professionals to the general public and have a lot to offer amid the COVID-19 response. This have led to significant changes in the health systems of many countries. This article seeks to highlight additional roles and activities relating to the public health response that can be undertaken by community pharmacists that could help to reduce pressure on general practice and other areas of the health service.

negative: COVID-19 in a Long-Term Care Facility - King County, Washington, February 27-March 9, 2020. On February 28, 2020, a case of coronavirus disease (COVID-19) was identified in a woman resident of a long-term care skilled nursing facility (facility A) in King County, Washington.* Epidemiologic investigation of facility A identified 129 cases of COVID-19 associated with facility A, including 81 of the residents, 34 staff members, and 14 visitors; 23 persons died. Limitations in effective infection control and prevention and staff members working in multiple facilities contributed to intra- and interfacility spread. COVID-19 can spread rapidly in long-term residential care facilities, and persons with chronic underlying medical conditions are at greater risk for COVID-19-associated severe disease and death. Long-term care facilities should take proactive steps to protect the health of residents and preserve the health care workforce by identifying and excluding potentially infected staff members and visitors, ensuring early recognition of potentially infected patients, and implementing appropriate infection control measures.

negative: Strategies for Successful Catheterization Laboratory Recovery From the COVID-19 Pandemic ABSTRACT As the world slowly starts to recover from the COVID-19 pandemic, healthcare systems are now thinking about resuming elective cardiovascular procedures, including procedures in the cardiac catheterization laboratories (cath lab). Rebooting cath labs will be an arduous process in part due to limited healthcare resources, new processes and fears stemming from the COVID-19 pandemic. We propose a detailed phased-in approach that considers clinical, patient-centered, and operational strategies to safely and effectively reboot cath lab programs during these unprecedented times. This model balances delivery of essential cardiovascular care while reducing exposure and preserving resources. The guiding principles detailed in this manuscript can be used by cath lab programs when restarting elective interventional procedures.

negative: Understanding Epidemic Data and Statistics: A case study of COVID-19 The 2019-Novel-Coronavirus (COVID-19) has affected 181 countries and out of about 1197405 confirmed cases (By April 5). Understanding the transmission dynamics of the infection in each country which affected on a daily basis and evaluating the effectiveness of control policies is critical for our further actions. To date, the statistics of COVID-19 reported cases show more than 80 percent of infected had a mild case of disease, while around 14 percent of infected experienced a severe one and about 5 percent are categorized as critical disease victims. Today's report (2020-04-05; daily updates in the prepared website) shows the confirmed cases of COVID-19 in the US, Spain, Italy, and Germany are 308850, 126168, 124632, and 96092; respectively. Calculating the total Case Fatality Rate (CFR) of Italy (2020-04-04), about 13.3% of confirmed cases passed away. Compared to South Korea's rate of 1.8% (7 times lower than Italy) and China's 4% (69% lower than Italy), the CFR of Italy is too high. There are some effective policies that yield significant changes in the trend of cases. The lockdown policy in China, Italy, and Spain (the effect observed after some days), Shutdown of all non-essential companies in Hubei (the effect observed after 5 days), combined policy in South Korea, and reducing working hours in Iran.

negative: Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients Over 1 000 000 cases of coronavirus disease 2019 (COVID‐19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID‐19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus–related hepatocellular carcinoma and was confirmed to have COVID‐19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low‐dose methylprednisolone‐based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living‐related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID‐19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID‐19. These effectively treated cases can provide a basis for immunosuppressant management of COVID‐19‐positive SOT recipients.

negative: The Perfect Moral Storm: Diverse Ethical Considerations in the COVID-19 Pandemic The COVID-19 pandemic has both exposed and created deep rifts in society. It has thrust us into deep ethical thinking to help justify the difficult decisions many will be called upon to make and to protect from decisions that lack ethical underpinnings. This paper aims to highlight ethical issues in six different areas of life highlighting the enormity of the task we are faced with globally. In the context of COVID-19, we consider health inequity, dilemmas in triage and allocation of scarce resources, ethical issues associated with research, ethical considerations relating to tracing apps, and exit strategies such as immunity passports and COVID-19 vaccines. Finally, we consider environmental issues in light of COVID-19. The paper also offers some ethical reflection on these areas as many parts of the world contemplate the recovery phase.

negative: High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019 The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomized studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.

negative: Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality Abstract Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world.

negative: The impact of believing you have had COVID-19 on behaviour: Cross-sectional survey Objectives: To investigate whether people who think they have had COVID-19 are less likely to engage in social distancing measures compared with those who think they have not had COVID-19. Design: On-line cross-sectional survey. Setting: Data were collected between 20th and 22nd April. Participants: 6149 participants living in the UK aged 18 years or over. Main outcome measures: Perceived immunity to COVID-19, self-reported adherence to social distancing measures (going out for essential shopping, nonessential shopping, and meeting up with friends/family; total out-of-home activity), worry about COVID-19 and perceived risk of COVID-19 to oneself and people in the UK. Knowledge that cough and high temperature / fever are the main symptoms of COVID-19. Results: In this sample, 1493 people (24.3%) thought they had had COVID-19. Only 245 (4.0%) reported receiving a test result saying they had COVID-19. Reported test results were often incongruent with participants' belief that they had had COVID-19. People who believed that they had had COVID-19 were: more likely to agree that they had some immunity to COVID-19; less likely to report adhering to social distancing measures; less worried about COVID-19; and less likely to know that cough and high temperature / fever are two of the most common symptoms of COVID-19. Conclusions: The number of people in the UK who think they have already had COVID-19 is about twice the rate of current prevalence estimates. People who think that they have had COVID-19 may contribute to transmission of the virus through non-adherence to social distancing measures. Clear communications to this growing group are needed to explain why protective measures continue to be important and to encourage sustained adherence.

negative: A Review of Cardiac Complications in Coronavirus Disease 2019 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has shown an association with acute myocardial injury, cardiomyopathy, and myocarditis. Individuals with myocardial involvement in association with the coronavirus disease 2019 (COVID-19) may be at increased risk of developing severe illness. Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. It has been primarily divided into three subsets: genetic, mixed, and acquired cardiomyopathy. We anticipate that, because of the high inflammatory response, other cardiovascular complications may also occur in COVID-19 patients with severe symptoms. This review explores new information as it pertains to COVID-19 and cardiac complications.

negative: Novel Insights Into Illness Progression and Risk Profiles for Mortality in Non-survivors of COVID-19 Background. The outbreak of COVID-19 has attracted the attention of the whole world. Our study aimed to describe illness progression and risk profiles for mortality in non-survivors. Methods. We retrospectively analyzed 155 patients with COVID-19 in Wuhan and focused on 18 non-survivors among them. Briefly, we compared the dynamic profile of biochemical and immune parameters and drew an epidemiological and clinical picture of disease progression from disease onset to death in non-survivors. The survival status of the cohort was indicated by a Kaplan–Meier curve. Results. Of the non-survivors, the median age was 73.5 years, and the proportion of males was 72.2%. Five and 13 patients were hospital-acquired and community-acquired infection of SARS-CoV-2, respectively. The interval between disease onset and diagnosis was 8.5 days (IQR, [4–11]). With the deterioration of disease, most patients experienced consecutive changes in biochemical parameters, including lymphopenia, leukocytosis, thrombocytopenia, hypoproteinemia, as well as elevated D-dimer and procalcitonin. Regarding the immune dysregulation, patients exhibited significantly decreased T lymphocytes in the peripheral blood, including CD3(+)T, CD3(+)CD4(+)Th, and CD3(+)CD8(+)Tc cells. By the end of the disease, most patients suffered from severe complications, including ARDS (17/18; 94.4%), acute cardiac injury (10/18; 55.6%), acute kidney injury (7/18; 38.9%), shock (6/18; 33.3%), gastrointestinal bleeding (1/18; 5.6%), as well as perforation of intestine (1/18; 5.6%). All patients died within 45 days after the initial hospital admission with a median survivor time of 13.5 days (IQR, 8–17). Conclusions. Our data show that patients experienced consecutive changes in biochemical and immune parameters with the deterioration of the disease, indicating the necessity of early intervention.

negative: A scientometric overview of CORD-19 As the COVID-19 pandemic unfolds, researchers from all disciplines are coming together and contributing their expertise. CORD-19, a dataset of COVID-19 and coronavirus publications, has recently been published alongside calls to help mine the information it contains, and to create tools to search it more effectively. Here, we focus on the delineation of the publications included in CORD-19, and analyse this delineation from a scientometric perspective. We find that CORD-19 contains research not only on COVID-19 and coronaviruses, but on viruses in general. Publications from CORD-19 mostly focus on a few, well-defined areas, including: coronaviruses (primarily SARS, MERS, COVID-19); public health and viral epidemics; the molecular biology of viruses; influenza and other families of viruses; immunology and antivirals; methodology (testing, diagnosing, clinical trials). CORD-19 publications published in 2020, especially focused on topics of pressing relevance (spread, infection, efficacy of counter-measures), are disproportionately popular on social media. While we fully endorse the initiative that led to CORD-19, we also advise to consider its relatively broad content critically.

negative: COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

negative: Assessment of Health Information About COVID-19 Prevention on the Internet: Infodemiological Study BACKGROUND: The internet is a large source of health information and has the capacity to influence its users. However, the information found on the internet often lacks scientific rigor, as anyone may upload content. This factor is a cause of great concern to scientific societies, governments, and users. OBJECTIVE: The objective of our study was to investigate the information about the prevention of coronavirus disease 2019 (COVID-19) on the internet. METHODS: On February 29, 2020, we performed a Google search with the terms “Prevention coronavirus,” “Prevention COVID-19,” “Prevención coronavirus,” and “Prevención COVID-19”. A univariate analysis was performed to study the association between the type of authorship, country of publication, and recommendations to avoid COVID-19 according to the World Health Organization (WHO). RESULTS: In total, 80 weblinks were reviewed. Most of them were produced in the United States and Spain (n=58, 73%) by digital media sources and official public health organizations (n=60, 75%). The most mentioned WHO preventive measure was “wash your hands frequently” (n=65, 81%). A less frequent recommendation was to “stay home if you feel unwell” (n=26, 33%). The analysis by type of author (official public health organizations versus digital media) revealed significant differences regarding the recommendation to wear a mask when you are healthy only if caring for a person with suspected COVID-19 (odds ratio [OR] 4.39). According to the country of publication (Spain versus the United States), significant differences were detected regarding some recommendations such as “wash your hands frequently” (OR 9.82), “cover your mouth and nose with your bent elbow or tissue when you cough or sneeze” (OR 4.59), or “stay home if you feel unwell” (OR 0.31). CONCLUSIONS: It is necessary to urge and promote the use of the websites of official public health organizations when seeking information on COVID-19 preventive measures on the internet. In this way, users will be able to obtain high-quality information more frequently, and such websites may improve their accessibility and positioning, given that search engines justify the positioning of links obtained in a search based on the frequency of access to them.

negative: Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020 An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January–February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1–7). Our findings suggest that R(t) decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of R(t) reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

negative: The Australian Institute of Sport Framework for Rebooting Sport in a COVID-19 Environment Abstract Sport makes an important contribution to the physical, psychological and emotional well-being of Australians. The economic contribution of sport is equivalent to 2–3% of Gross Domestic Product (GDP). The COVID-19 pandemic has had devastating effects on communities globally, leading to significant restrictions on all sectors of society, including sport. Resumption of sport can significantly contribute to the re-establishment of normality in Australian society. The Australian Institute of Sport (AIS), in consultation with sport partners (National Institute Network (NIN) Directors, NIN Chief Medical Officers (CMOs), National Sporting Organisation (NSO) Presidents, NSO Performance Directors and NSO CMOs), has developed a framework to inform the resumption of sport. National Principles for Resumption of Sport were used as a guide in the development of ‘the AIS Framework for Rebooting Sport in a COVID-19 Environment’ (the AIS Framework); and based on current best evidence, and guidelines from the Australian Federal Government, extrapolated into the sporting context by specialists in sport and exercise medicine, infectious diseases and public health. The principles outlined in this document apply to high performance/professional, community and individual passive (non-contact) sport. The AIS Framework is a timely tool of minimum baseline of standards, for ‘how’ reintroduction of sport activity will occur in a cautious and methodical manner, based on the best available evidence to optimise athlete and community safety. Decisions regarding the timing of resumption (the ‘when’ ) of sporting activity must be made in close consultation with Federal, State/Territory and Local Public Health Authorities. The priority at all times must be to preserve public health, minimising the risk of community transmission.

negative: Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines The coronavirus disease (COVID-19) pandemic has led to a global struggle to cope with the sheer numbers of infected persons, many of whom require intensive care support or eventually succumb to the illness. The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected. To date, there is no specific anti-COVID-19 treatment. However, the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome, especially in the severe to critically ill. While many of these adjunctive drugs are being investigated in clinical trials, professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use. This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.

negative: A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and herpesvirus sequences that were widespread throughout Neoromicia populations in South Africa. Furthermore, similar adenovirus sequences were detected within these populations throughout several years. With the exception of the coronaviruses, the study represents the first report of sequence data from several viral families within a Southern African insectivorous bat genus; highlighting the need for continued investigations in this regard.

negative: Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review Objectives: To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design: This study is a review. Data sources: Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria: Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered.Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis: The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results: 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion: Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Keywords: Outcomes; clinical trials, COVID-19; review.

negative: Neurobiology of COVID-19 Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19 who may present with acute neurological symptoms (e.g., stroke), even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic "NeuroCovid" classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the long-term sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson's disease, or Alzheimer's disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system.

negative: Abstract of 29th Regional Congress of the ISBT

negative: Data-based analysis, modelling and forecasting of the COVID-19 outbreak Since the first suspected case of coronavirus disease-2019 (COVID-19) on December 1st, 2019, in Wuhan, Hubei Province, China, a total of 40,235 confirmed cases and 909 deaths have been reported in China up to February 10, 2020, evoking fear locally and internationally. Here, based on the publicly available epidemiological data for Hubei, China from January 11 to February 10, 2020, we provide estimates of the main epidemiological parameters. In particular, we provide an estimation of the case fatality and case recovery ratios, along with their 90% confidence intervals as the outbreak evolves. On the basis of a Susceptible-Infectious-Recovered-Dead (SIDR) model, we provide estimations of the basic reproduction number (R(0)), and the per day infection mortality and recovery rates. By calibrating the parameters of the SIRD model to the reported data, we also attempt to forecast the evolution of the outbreak at the epicenter three weeks ahead, i.e. until February 29. As the number of infected individuals, especially of those with asymptomatic or mild courses, is suspected to be much higher than the official numbers, which can be considered only as a subset of the actual numbers of infected and recovered cases in the total population, we have repeated the calculations under a second scenario that considers twenty times the number of confirmed infected cases and forty times the number of recovered, leaving the number of deaths unchanged. Based on the reported data, the expected value of R(0) as computed considering the period from the 11th of January until the 18th of January, using the official counts of confirmed cases was found to be ∼4.6, while the one computed under the second scenario was found to be ∼3.2. Thus, based on the SIRD simulations, the estimated average value of R(0) was found to be ∼2.6 based on confirmed cases and ∼2 based on the second scenario. Our forecasting flashes a note of caution for the presently unfolding outbreak in China. Based on the official counts for confirmed cases, the simulations suggest that the cumulative number of infected could reach 180,000 (with a lower bound of 45,000) by February 29. Regarding the number of deaths, simulations forecast that on the basis of the up to the 10th of February reported data, the death toll might exceed 2,700 (as a lower bound) by February 29. Our analysis further reveals a significant decline of the case fatality ratio from January 26 to which various factors may have contributed, such as the severe control measures taken in Hubei, China (e.g. quarantine and hospitalization of infected individuals), but mainly because of the fact that the actual cumulative numbers of infected and recovered cases in the population most likely are much higher than the reported ones. Thus, in a scenario where we have taken twenty times the confirmed number of infected and forty times the confirmed number of recovered cases, the case fatality ratio is around ∼0.15% in the total population. Importantly, based on this scenario, simulations suggest a slow down of the outbreak in Hubei at the end of February.

negative: Detection of transmissible gastroenteritis virus by RT-PCR and differentiation from porcine respiratory coronavirus Abstract An RT-PCR method was developed that amplified genetic material from the 5′ end of the S protein gene of both transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV), but discriminated between the two by the size of the product generated. A number of restriction endonuclease enzymes were assessed for recognition of the amplicons so produced. The assay was shown to detect viral RNA from all of the 26 different TGEV and PRCV isolates examined, covering a period from 1946 to 1996. Detection of TGEV in clinical specimens was possible using a spin column method to extract RNA and sensitivity was compared to virus isolation and antigen detection ELISA. The method could provide a means of confirming positive results from immunological screening tests such as FAT and ELISA, reducing the need for virus isolation and convalescent serology.

negative: Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications Background The COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. Methods Plasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. Findings SARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. Interpretation The variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

negative: Successful Treatment of Severe COVID-19 Pneumonia in a Liver Transplant Recipient. Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.

negative: Schneller Ausstieg oder bedachte Lockerung?: Zur Zukunft von Kontaktbeschränkungen in der COVID-19-Krise How important is the relaxation of contact restrictions for the recovery of the German economy and what conclusions can be drawn for the appropriate level of contact restrictions in the coming months? In considering these issues, an attempt will be made to assess what significance the contact restriction measures introduced by the federal and state governments since mid-March 2020 will actually have for the current slump in economic activity in Germany. In addition, the various plausible scenarios for the spread and containment of infection are presented with different options for easing contact restrictions.

negative: CoVDB: a comprehensive database for comparative analysis of coronavirus genes and genomes The recent SARS epidemic has boosted interest in the discovery of novel human and animal coronaviruses. By July 2007, more than 3000 coronavirus sequence records, including 264 complete genomes, are available in GenBank. The number of coronavirus species with complete genomes available has increased from 9 in 2003 to 25 in 2007, of which six, including coronavirus HKU1, bat SARS coronavirus, group 1 bat coronavirus HKU2, groups 2c and 2d coronaviruses, were sequenced by our laboratory. To overcome the problems we encountered in the existing databases during comparative sequence analysis, we built a comprehensive database, CoVDB (http://covdb.microbiology.hku.hk), of annotated coronavirus genes and genomes. CoVDB provides a convenient platform for rapid and accurate batch sequence retrieval, the cornerstone and bottleneck for comparative gene or genome analysis. Sequences can be directly downloaded from the website in FASTA format. CoVDB also provides detailed annotation of all coronavirus sequences using a standardized nomenclature system, and overcomes the problems of duplicated and identical sequences in other databases. For complete genomes, a single representative sequence for each species is available for comparative analysis such as phylogenetic studies. With the annotated sequences in CoVDB, more specific blast search results can be generated for efficient downstream analysis.

negative: Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019 Abstract The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.

negative: Dynamics of Interacting Hotspots - II In the absence of any proper clinical solution, human civilization is only left with sophisticated intervention measures to contain the spread of COVID-19. However, the existing models to estimate the intervention does not take into account the realistic connectivity of the epicentres of the pandemic. We generalise our earlier model of interacting hotspots to test various possibilities of intervention in a model state consisting of multiple epicentres. We also analyse situations when the hotspots are spatially correlated and the interaction is limited to population exchanges with the nearest neighbours. We show that the heterogeneity in the infection propagation is solely dependent on the protocol of the containment and its strength. We explore many such situations and discuss possibilities.

negative: Addiction psychiatry and COVID-19: impact on patients and service provision The Coronavirus Disease 2019 (COVID-19) pandemic has undoubtedly had a major impact on the provision of physical healthcare in Ireland and worldwide. The mental health impact of this pandemic cannot be underestimated, particularly relating to patients suffering from addiction. Heightened public stress and anxiety levels, increasing isolation and the physical consequences of addiction play a large role in the proliferation and ongoing relapse of substance misuse and behavioural addiction. Service provision is an ongoing challenge not only due to the increasing need for services given the increased mental health burden of COVID-19 but also the restrictions in place in clinical areas to achieve social distancing. The necessary adaptations to service provision provide opportunities for the analysis of current processes used in our addiction unit and the introduction of new processes to our service. The current crisis tests the sustainability of the service to provide the high standard of care required for these patients.

negative: A current review of COVID-19 for the cardiovascular specialist Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.

negative: Clinical features, Diagnosis, and Treatment of COVID-19: A systematic review of case reports and case series Objectives: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, Web of Science and the Cochrane Library to collect both case reports and case series on COVID-19 published up to February 30, 2020. Results: Thirty-four articles were included analyzing a total of 99 patients with a mean age of 46.2 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 83% of patients from 76.4% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies which reported C-reactive protein (CRP) measurements (44%), a large majority of patients displayed an elevated CRP (73%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (33%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (71.0%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for presence and severity of disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.

negative: Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review Background: Since early December 2019, the Coronavirus Disease 19 (COVID-19) infection has been prevalent in China and eventually spread to other countries. There are a few published cases of COVID-19 occurring during pregnancy and due the possibility of mother-fetal vertical transmission, there is a concern that the fetuses may be at risk of congenital COVID-19. Methods: We reviewed the risk of vertical transmission of COVID-19 to the fetus of infected mothers by using data of published articles or official websites up to March 4, 2020. Results: A total of 31 infected pregnant mothers with COVID-19 were reported. No COVID-19 infection was detected in their neonates or placentas. Two mothers died from COVID-19-related respiratory complications after delivery. Conclusions: Currently, based on limited data, there is no evidence for intrauterine transmission of COVID-19 from infected pregnant women to their fetuses. Mothers may be at increased risk for more severe respiratory complications.

negative: Remdesivir for the Treatment of Covid-19 — Preliminary Report BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

negative: Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study [Image: see text] The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson–Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev.2019, 119, 947831244000; Wang, Curr. Comput.-Aided Drug Des.2006, 2, 287; Wang; HouJ. Chem. Inf. Model., 2012, 52, 119922497310). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, −13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (−3.8 kcal/mol) is not nearly as low as that of the neutral form (−7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of −12.9 kcal/mol. Detailed receptor–ligand interactions were analyzed and hot spots for the receptor–ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.

negative: Early experience with convalescent plasma as immunotherapy for COVID‐19 in China: Knowns and unknowns BACKGROUND AND OBJECTIVES: In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID‐19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID‐19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID‐19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti‐epidemic strategy. MATERIALS AND METHODS: As of May 5, 2020, when the epidemic was well‐controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. RESULTS: As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID‐19 patients. From donors, 200–400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID‐19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. CONCLUSION: From initial studies, convalescent plasma therapy appears effective and safe for COVID‐19. However, there is clearly a need for well‐designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.

negative: Critical community size for COVID-19 -- a model based approach to provide a rationale behind the lockdown Background: Restrictive mass quarantine or lockdown has been implemented as the most important controlling measure to fight against COVID-19. Many countries have enforced 2 - 4 weeks' lockdown and are extending the period depending on their current disease scenario. Most probably the 14-day period of estimated communicability of COVID-19 prompted such decision. But the idea that, if the susceptible population drops below certain threshold, the infection would naturally die out in small communities after a fixed time (following the outbreak), unless the disease is reintroduced from outside, was proposed by Bartlett in 1957. This threshold was termed as Critical Community Size (CCS). Methods: We propose an SEIR model that explains COVID-19 disease dynamics. Using our model, we have calculated country-specific expected time to extinction (TTE) and CCS that would essentially determine the ideal number of lockdown days required and size of quarantined population. Findings: With the given country-wise rates of death, recovery and other parameters, we have identified that, if at a place the total number of susceptible population drops below CCS, infection will cease to exist after a period of TTE days, unless it is introduced from outside. But the disease will almost die out much sooner. We have calculated the country-specific estimate of the ideal number of lockdown days. Thus, smaller lockdown phase is sufficient to contain COVID-19. On a cautionary note, our model indicates another rise in infection almost a year later but on a lesser magnitude.

negative: STEMI care during COVID-19: losing sight of the forest for the trees [Figure: see text]

negative: COVID-19: One-month impact of the French lockdown on the epidemic burden On March 16 2020, French authorities ordered a large scale lockdown to counter the COVID-19 epidemic wave rising in the country, stopping non-essential economic, educational, and entertainment activities, maintaining mainly food retailers and healthcare institutions. One month later, the number of new hospitalizations and ICU admissions had reached a plateau and were beginning a slow descent. We developed a spatialized, deterministic, age-structured, and compartmental SARS-CoV-2 transmission model able to reproduce the pre-lockdown dynamic of the epidemic in each of the 13 French metropolitan regions. Thanks to this model, we estimate, at regional and national levels, the total number of hospitalizations, ICU admissions, hospital beds requirements (hospitalization and ICU), and hospital deaths which may have been prevented by this massive and unprecedented intervention in France. If no control measures had been set up, between March 19 and April 19 2020, our analysis shows that almost 23% of the French population would have been affected by COVID-19 (14.8 million individuals). Hence, the French lockdown prevented 587,730 hospitalizations and 140,320 ICU admissions at the national level. The total number of ICU beds required to treat patients in critical conditions would have been 104,550, far higher than the maximum French ICU capacity. This first month of lockdown also permitted to avoid 61,739 hospital deaths, corresponding to a 83.5% reduction of the total number of predicted deaths. Our analysis shows that in absence of any control measures, the COVID-19 epidemic would have had a critical morbidity and mortality burden in France, overwhelming in a matter of weeks French hospital capacities.

negative: RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.

negative: Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia/ 中华临床感染病杂志 Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

negative: Preliminary evaluation of COVID-19 disease outcomes, test capacities and management approaches among African countries. Background: Following the declaration of COVID-19 as a global pandemic and the report of index case in Africa, the number of countries in Africa with confirmed cases of the infection has grown tremendously with disease now being reported in almost all countries on the continent, with the exemption of Lesotho after 75 days. It is therefore necessary to evaluate the disease outcomes among the African countries as the situation unfolds for early identification of best practices for adoption. Methods: In this study, COVID-19 disease outcomes (confirmed cases, deaths and recoveries), testing capacities and disease management approaches among African countries were evaluated. The relationship between COVID-19 infections in African countries and their performance on global resilient indices including the Human Development Index (HDI), performance on Sustainable Development Goals (SDGs) and the Global Risk Index (GRI) were also examined. Data acquired from various standard databases were evaluated over a period of 75 days from the date of reporting the index case. Results: This study has revealed compelling spatial differences in the incidence, deaths and recoveries from COVID-19 among African countries. Egypt, South Africa, Morocco and Algeria were clustered as countries with highest values of COVID-19 disease outcomes on the continent during the 75-day period of observation. The cluster analysis and comparison of countries in terms of percentage recovered cases of confirmed infections revealed that Mauritius, Mauritania, Gambia, Burkina Faso, Madagascar, Togo and Uganda had the highest scores. Comparative analysis of COVID-19 across the world revealed that the parameters were relatively inconsequential in Oceania and Africa continents, while Europe, North America and Asia had significantly higher cases of disease outcomes. For COVID-19 testing capacities, South Africa, Ghana and Egypt are leading in total number of tests carried out. However when the number of tests carried out were related to population number of the countries, Djibouti, Mauritius, Ghana and South Africa are found to be the leading countries. With respect to management of the disease in Africa, all the countries adopted the WHO protocols, personal hygiene, economic palliatives and social distancing measures. Only three countries in Africa (Madagascar, Togo and Burkina Faso) had a state supported initiative to utilise traditional medicines or herbs as alternatives to control COVID-19. Additionally, most of the countries are providing prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study found that no strong relationship currently exists between the global resilient indicators (HDI, SDG and GRI) and COVID-19 cases across Africa. Conclusions: This study has revealed compelling spatial differences in disease outcomes among African countries and also found testing capacities for COVID-19 to be abysmally low in relation to the population. During the 75 days of observation, African countries have recorded significantly low number of deaths associated with COVID-19 and relatively high recovery rates. Countries in Africa with higher rate of recovery from the disease were found to have adopted strict adherence to some of WHO protocol to contain the disease, isolate all those who test positive to the disease and provide prompt treatment of the patients with a range of drugs especially Hydroxychloroquine, Chloroquine and Chloroquine-Azithromycin combination. The study recommends that the approaches adopted by the African countries which achieved high recovery rates from COVID-19 should be integrated into healthcare management plans for the disease across the continent even as the situation unfolds.

negative: Therapeutic Management of COVID-19 Patients: A systematic review Abstract Background SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1st , 2019 to March 26th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results As of March 26th, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16). Conclusions This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. Corticosteroid therapy was found to be the most studied medicine in the literature.

negative: Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.

negative: Mortality Rate of Infection With COVID-19 in Korea From the Perspective of Underlying Disease On December 31, 2019 the China National Health Commission (NHC) reported that an unknown cause of pneumonia had been detected in Wuhan in Hubei province. On February 12, the disease caused by the novel coronavirus (2019-nCoV) was given a formal name, COVID-19. On January 20, 2020, the first case of COVID-19 was confirmed in Korea. The age-specific death rate was the highest among patients over 70 years of age, with underlying diseases in their circulatory system, such as myocardial infarction, cerebral infraction, arrythmia, and hypertension. Patients with underlying disease who are 70 years of age or older should recognize that there is a high possibility of developing a serious disease in case of viral infection and follow strict precautions.

negative: Endpoints for randomized controlled clinical trials for COVID-19 treatments Introduction: Endpoint choice for randomized controlled trials of treatments for COVID-19 is complex. A new disease brings many uncertainties, but trials must start rapidly. COVID-19 is heterogeneous, ranging from mild disease that improves within days to critical disease that can last weeks and can end in death. While improvement in mortality would provide unquestionable evidence about clinical significance of a treatment, sample sizes for a study evaluating mortality are large and may be impractical. Furthermore, patient states in between"cure"and"death"represent meaningful distinctions. Clinical severity scores have been proposed as an alternative. However, the appropriate summary measure for severity scores has been the subject of debate, particularly in relating to the uncertainty about the time-course of COVID-19. Outcomes measured at fixed time-points may risk missing the time of clinical benefit. An endpoint such as time-to-improvement (or recovery), avoids the timing problem. However, some have argued that power losses will result from reducing the ordinal scale to a binary state of"recovered"vs"not recovered."Methods: We evaluate statistical power for possible trial endpoints for COVID-19 treatment trials using simulation models and data from two recent COVID-19 treatment trials. Results: Power for fixed-time point methods depends heavily on the time selected for evaluation. Time-to-improvement (or recovery) analyses do not specify a time-point. Time-to-event approaches have reasonable statistical power, even when compared to a fixed time-point method evaluated at the optimal time. Discussion: Time-to-event analyses methods have advantages in the COVID-19 setting, unless the optimal time for evaluating treatment effect is known in advance. Even when the optimal time is known, a time-to-event approach may increase power for interim analyses.

negative: CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo axial diffusivity BACKGROUND: Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE. METHODS: C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant. RESULTS: In vivo DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of naïve and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with axial diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial diffusivity values. Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls. CONCLUSIONS: These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.

negative: The impact of the COVID-19 pandemic on suicide rates Multiple lines of evidence indicate that the COVID-19 pandemic has profound psychological and social effects. The psychological sequelae of the pandemic will probably persist for months and years to come. Studies indicate that the COVID-19 pandemic is associated with distress, anxiety, fear of contagion, depression, and insomnia in the general population and among health care professionals. Social isolation, anxiety, fear of contagion, uncertainty, chronic stress, and economic difficulties may lead to the development or exacerbation of depressive, anxiety, substance use, and other psychiatric disorders in vulnerable populations including individuals with pre-existing psychiatric disorders and people who reside in high COVID-19 prevalence areas. Stress-related psychiatric conditions including mood and substance use disorders are associated with suicidal behavior. COVID-19 survivors may also be at elevated suicide risk. The COVID-19 crisis may increase suicide rates during and after the pandemic. Mental health consequences of the COVID-19 crisis including suicidal behavior are likely to be present for a long time and peak later than the actual pandemic. To reduce suicides during the COVID-19 crisis it is imperative to decrease stress, anxiety, fears and loneliness in the general population. There should be traditional and social media campaigns to promote mental health and reduce distress. Active outreach is necessary, especially for people with a history of psychiatric disorders, COVID-19 survivors, and older adults. Research studies are needed of how mental health consequences can be mitigated during and after the COVID-19 pandemic.

negative: Signals of T(h)2 immune response from COVID-19 patients requiring intensive care

negative: Coronavirus disease 2019 (COVID-19) and cardiovascular complications Abstract The coronavirus disease 2019 (COVID-19) has become a global pandemic. It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.

negative: Coronavirus Disease (COVID-19) in Italy: Analysis of Risk Factors and Proposed Remedial Measures

negative: COVID-19: Beyond the virus. The use of Photodynamic Therapy for the Treatment of Infections in the Respiratory Tract

negative: Mesenchymal Stem Cell Infusion Shows Promise for Combating Coronavirus (COVID-19)- Induced Pneumonia A new study published by the journal Aging & Disease reported that intravenous administration of clinical-grade human mesenchymal stem cells (MSCs) into patients with coronavirus disease 2019 (COVID-19) resulted in improved functional outcomes (Leng et al., Aging Dis, 11:216-228, 2020). This study demonstrated that intravenous infusion of MSCs is a safe and effective approach for treating patients with COVID-19 pneumonia, including elderly patients displaying severe pneumonia. COVID-19 is a severe acute respiratory illness caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, treating COVID-19 patients, particularly those afflicted with severe pneumonia, is challenging as no specific drugs or vaccines against SARS-CoV-2 are available. Therefore, MSC therapy inhibiting the overactivation of the immune system and promoting endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection found in this study is striking. Additional studies in a larger cohort of patients are needed to validate this therapeutic intervention further, however.

negative: Epizootic diarrhoea of adult cattle associated with a coronavirus-like agent Abstract An epizootic of acute diarrhoea of adult cattle occured in Japan during the winter of 1976 to 1977. A majority of adult cattle clinically diagnosed as having the disease, showed a significant rises in antibody titres to bovine coronavirus, whereas only a smal; minority showed serological evidence of recent infection with calf rotavirus, bovine adenovirus type 7, parainfluenza virus type 3, or bovine viral diarrhoea-mucosal disease virus. A coronavirus-like agent was detected by electron-microscopy in faecal material from a cow with diarrhoea, and was subsequently isolated in primary bovine kidney cell cultures.

negative: Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China BACKGROUND: In late December 2019, an outbreak of acute respiratory illness, coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. We aimed to study the epidemiology, clinical features and short-term outcomes of patients with COVID-19 in Wuhan, China. METHODS: We performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital, including 55 severe patients and 166 non-severe patients, from January 2, 2020 to February 10, 2020. RESULTS: Of the 221 patients with COVID-19, the median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU (intensive care unit) care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. CONCLUSIONS: Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

negative: COVID-19 and diabetes mellitus: A need for prudence in elderly patients from a pooled analysis OBJECTIVE: The objective of this study was to evaluate the pooled estimate of diabetes prevalence in young (<50 years) versus elderly (>50 years) COVID-19 cohorts. METHODS: Studies published between December-2019 and March-2020 reporting demographic and clinical characteristics of COVID-19 cases were identified. A total of 11 studies included accounting for 2084 COVID-19 patients. RESULTS: The overall prevalence of diabetes in COVID-19 patients with a mean age>50 years was 13.2%, whereas studies with relatively younger patients (mean age <50 years) had a pooled prevalence of 9.0% CONCLUSION: The overall prevalence of diabetes in COVID-19 patients was found to be 13.2%. The intermingled effects of diabetes with other cardiovascular comorbidities warrant age-specific outcomes data including the impact of ongoing antidiabetic treatment.

negative: Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children.

negative: Acute myocarditis associated with novel Middle East respiratory syndrome coronavirus The novel Middle East respiratory syndrome coronavirus (MERS-CoV) has been identified as a cause of pneumonia; however, it has not been reported as a cause of acute myocarditis. A 60-year-old man presented with pneumonia and congestive heart failure. On the first day of admission, he was found to have an elevated troponin-I level and severe global left ventricular systolic dysfunction on echocardiography. The serum creatinine level was found mildly elevated. Chest radiography revealed in the lower lung fields accentuated bronchovascular lung markings and multiple small patchy opacities. Laboratory tests were negative for viruses known to cause myocarditis. Sputum sample was positive for MERS-CoV. Cardiovascular magnetic resonance revealed evidence of acute myocarditis. The patient had all criteria specified by the International Consensus Group on CMR in Myocarditis that make a clinical suspicion for acute myocarditis. This was the first case that demonstrated that MERS-CoV may cause acute myocarditis and acute-onset heart failure.

negative: Statistical analysis and visualization of the potential cases of pandemic coronavirus A local outbreak of initially unknown cause pneumonia was detected in Wuhan (Hubei, China) in December 2019 and a novel coronavirus, the severe acute respiratory syndrome coronavirus 2, was quickly found to be causing it. Since then, the epidemic has spread to all of China's mainland provinces as well as 58 other countries and territories, with more than 87,137 confirmed cases around the globe, including 79,968 from China, 7169 from other countries as of 1 March 2020, as stated by the World Health Organization in the COVID-19 situation report-41. In response to this current public health emergency, this study done a statistical analysis and visualized reported cases of coronavirus disease 2019 (COVID-19) based on the open data collection provided by Johns Hopkins University. Where the location and number of confirmed infected cases have been shown, there have also been deaths, recovered cases and comparisons of the growth rates between the Globe countries. This was intended to provide researchers, public health officials and the general public with exposure to the epidemic.

negative: Current and future therapeutical approaches for COVID-19 • COVID-19, an alarming pandemic outbreak of 2020. • Amelioration of the clinical understanding of COVID-19 and its potential targets. • Adapted clinical strategies based on merits and demerits of COVID-19 treatment. • Current clinical manifestations and the proposed prospects against COVID-19. Coronavirus 2019 (COVID-19), the WHO-classified novel coronavirus of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global pandemic. To tackle both its spread and virulence, research is ongoing worldwide to develop an effective anti-COVID-19 drug or vaccine. In this review, we explore the clinical understanding and severity of COVID-19 emergence across the world, with a focus on China. We also discuss potential therapeutic targets, either host virus based, that could be used to tackle the COVID-19 outbreak.

negative: How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19 Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan–Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.

negative: Efficient Noise-Blind $\ell_1$-Regression of Nonnegative Compressible Signals In compressed sensing the goal is to recover a signal from as few as possible noisy, linear measurements. The general assumption is that the signal has only a few non-zero entries. Given an estimate for the noise level a common convex approach to recover the signal is basis pursuit denoising (BPDN). If the measurement matrix has the robust null space property with respect to the $\ell_2$-norm, BPDN obeys stable and robust recovery guarantees. In the case of unknown noise levels, nonnegative least squares recovers non-negative signals if the measurement matrix fulfills an additional property (sometimes called the $M^+$-criterion). However, if the measurement matrix is the biadjacency matrix of a random left regular bipartite graph it obeys with a high probability the null space property with respect to the $\ell_1$-norm with optimal parameters. Therefore, we discuss non-negative least absolute deviation (NNLAD). For these measurement matrices, we prove a uniform, stable and robust recovery guarantee. Such guarantees are important, since binary expander matrices are sparse and thus allow for fast sketching and recovery. We will further present a method to solve the NNLAD numerically and show that this is comparable to state of the art methods. Lastly, we explain how the NNLAD can be used for group testing in the recent COVID-19 crisis and why contamination of specimens may be modeled as peaky noise, which favors $\ell_1$ based data fidelity terms.

negative: Factors linked to changes in mental health outcomes among Brazilians in quarantine due to COVID-19 The 2020 COVID-19 pandemic is a crisis of global proportions with a significant impact on the country of Brazil. The aims of this investigation were to track changes and risk factors for mental health outcomes during state-mandated quarantine. Adults residing in Brazil (n = 360, 37.9 years of age, 68.9% female) were surveyed at the start of quarantine and 1 month later. Outcomes assessed included perceived stress, state anxiety and depression. Aside from demographics, behaviors and attitudes assessed included exercise, diet, use of tele-psychotherapy and number of COVID-19 related risk factors, such as perceived risk of COVID-19, information overload, and feeling imprisoned. Overall, all mental health outcomes worsened from Time 1 to time 2, although there was a significant gender x time interaction for stress. 9.7% of the sample reported stress above the clinical cut-off (2 SD above mean), while 8.0% and 9.4% were above this cutoff for depression and anxiety, respectively. In repeated measures analysis, female gender, worsening diet and excess of COVID-19 information was related to all mental health outcomes. Changes in diet for the worse were associated with increases in anxiety. Exercise frequency was clearly related to state anxiety (0 days/week > 6 days/week). Those who did aerobic exercise did not have any increase in depression. Use of tele-psychotherapy predicted lower levels of depression and anxiety. In multiple regression, anxiety was predicted by the greatest number of COVID-19 specific factors. In conclusion, mental health outcomes worsened for Brazilians during the first month of quarantine and these changes are associated with a variety of risk factors.

negative: Evidence Based Management Guideline for the COVID-19 Pandemic - Review article ABSTRACT COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 944,181 people worldwide, resulting in over 47,312 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.

negative: Effects of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcomes: a systematic review OBJECTIVE: To evaluate the effects of coronavirus disease 2019 (COVID‐19) on maternal, perinatal and neonatal outcomes by performing a systematic review of available published literature on pregnancies affected by COVID‐19. METHODS: We performed a systematic review to evaluate the effects of COVID‐19 on pregnancy, perinatal and neonatal outcomes. We conducted a comprehensive literature search using PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database and Wan Fang Data until 20 April 2020 (studies were identified through PubMed alert after that date). For the research strategy, combinations of the following keywords and MeSH terms were used: SARS‐CoV‐2, COVID‐19, coronavirus disease 2019, pregnancy, gestation, maternal, mothers, vertical transmission, maternal‐fetal transmission, intrauterine transmission, neonates, infant, delivery. Eligibility criteria included laboratory‐confirmed and/or clinically diagnosed COVID‐19, patient being pregnant on admission and availability of clinical characteristics, including at least one maternal, perinatal or neonatal outcome. Exclusion criteria were non‐peer‐reviewed or unpublished reports, unspecified date and location of the study, suspicion of duplicate reporting, and unreported maternal or perinatal outcomes. No language restrictions were applied. RESULTS: We identified a high number of relevant case reports and case series, but only 24 studies, including a total of 324 pregnant women with COVID‐19, met the eligibility criteria and were included in the systematic review. These comprised nine case series (eight consecutive) and 15 case reports. A total of 20 pregnant patients with laboratory‐confirmed COVID‐19 were included in the case reports. In the combined data from the eight consecutive case series, including 211 (71.5%) cases of laboratory‐confirmed and 84 (28.5%) of clinically diagnosed COVID‐19, the maternal age ranged from 20 to 44 years and the gestational age on admission ranged from 5 to 41 weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath, fatigue and myalgia. The rate of severe pneumonia reported amongst the case series ranged from 0 to 14%, with the majority of the cases requiring admission to the intensive care unit. Almost all cases from the case series had positive computer tomography chest findings. All six and 22 cases that had nucleic‐acid testing in vaginal mucus and breast milk samples, respectively, were negative for SARS‐CoV‐2. Only four cases of spontaneous miscarriage or abortion were reported. In the consecutive case series, 219/295 women had delivered at the time of reporting, and the majority of these had Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at 1 and 5 min ranged from 7 to 10 and 7 to 10, respectively. Only eight neonates had birth weight <2500 g and nearly one‐third of cases were transferred to the neonatal intensive care unit. There was one case each of neonatal asphyxia and neonatal death. In 155 neonates that had nucleic‐acid testing in throat swab, all, except three cases, were negative for SARS‐CoV‐2. There were seven maternal deaths, four intrauterine fetal deaths (one with twin pregnancy) and two neonatal deaths (twin pregnancy) reported in a non‐consecutive case series of nine cases with severe COVID‐19. From the case reports, two maternal deaths, one neonatal death and two cases of neonatal SARS‐CoV‐2 infection were reported. CONCLUSIONS: Despite the increasing number of published studies on COVID‐19 in pregnancy, there are insufficient good‐quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID‐19 in pregnant women, as well as vertical transmission, perinatal and neonatal complications. In order to answer specific questions in relation to the impact of COVID‐19 on pregnant women and their fetuses through meaningful good‐quality research, we urge researchers and investigators to present complete outcome data and reference previously published cases in their publications, and to record such reporting when the data of a case are entered into a registry or several registries. This article is protected by copyright. All rights reserved.

negative: What outcomes are important in the assessment of Enhanced Recovery After Surgery (ERAS) pathways? PURPOSE The purpose of this narrative review is to provide a framework from which to measure the outcomes of Enhanced Recovery After Surgery (ERAS) programs. PRINCIPLE FINDINGS We define the outcomes of recovery from the perspective of different stakeholders and time frames. There is no single definition of recovery. There are overlapping phases of recovery which are of particular interest to different stakeholders (surgeons, anesthesiologists, nurses, patients and their caregivers), and the primary outcome of interest may vary depending on the phase and the perspective. In the earliest phase (from the end of the surgery to discharge from the postanesthesia care unit [PACU]), biologic and physiologic outcomes are emphasized. In the intermediate phase (from PACU to discharge from the hospital), symptoms related to pain and gastrointestinal function as well as basic activities are important. Studies of ERAS pathways have reported clinical outcomes and symptoms, including complications, hospital stay, mobilization, and gastrointestinal function, largely during hospitalization. Nevertheless, patients define recovery as return to normal functioning, a process that occurs over weeks to months (late phase). Outcomes reflecting functional status (e.g., physical activity, activities of daily living) and overall health (e.g., quality of life) are important in this phase. To date, few studies reporting the effectiveness of ERAS pathways compared with conventional care have included functional status or quality-of-life outcomes, and there is little information about recovery after discharge from hospital. CONCLUSION Recovery after surgery is a complex construct. Different outcomes are important at different phases along the recovery trajectory. Measures for quantifying recovery in hospital and after discharge are available. A consensus-based core set of outcomes with input from multiple stakeholders would facilitate research reporting.

negative: The “Common Cold” in Frail Older Persons: Impact of Rhinovirus and Coronavirus in a Senior Daycare Center OBJECTIVE: To evaluate the incidence and impact of rhino‐virus and Coronavirus infections in older persons attending daycare. DESIGN: Prospective descriptive study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS: Frail older persons and staff members of the daycare centers who developed signs or symptoms of an acute respiratory illness MEASUREMENTS: Demographic, medical, and physical findings were recorded on subjects at baseline and during respiratory illness. Nasopharyngeal specimens for viral culture as well as acute and convalescent sera for Coronavirus 229E enzyme immunoassay (EIA) were obtained for all illnesses. RESULTS: During the 44 months of study, 352 older persons experienced 522 illnesses. Thirty‐five (7%) of 522 cultures were positive for rhinovirus and 37 (8%) of 451 serologies were positive for Coronavirus 229E infection. The clinical syndromes associated with rhinovirus and Coronavirus infection were similar and characterized by nasal congestion, cough, and constitutional symptoms. No patient died or was hospitalized, but approximately 50% had evidence of lower respiratory tract involvement. The average illness lasted 14 days. During the same period, 113 staff developed 338 respiratory illnesses. Eight percent were identified as Coronavirus and 9% as rhinovirus. Cough, sputum production, and constitutional symptoms were significantly more common among older persons. CONCLUSIONS: Rhinovirus and Coronavirus 229E are common causes of moderately debilitating acute respiratory illnesses among older persons attending daycare.

negative: Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): A systematic review Abstract Background The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusions Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.

negative: The UK Coronavirus Cancer Monitoring Project: protecting patients with cancer in the era of COVID-19

negative: Target Virus or Target Ourselves for COVID-19 Drugs Discovery?-Lessons learned from anti-influenzas virus therapies Abstract The COVID-19 pandemic, after it was reported in December 2019, is a highly contagious and now spreading to over 190 countries, causing a severe public health burden. Currently, there is no vaccine or specific drug to treat COVID-19, which is caused by a novel coronavirus, SARS-2-CoV. For this emergency, the FDA has approved Remdesivir and Hydroxychloroquine for treatment of COVID-19 as Emergency Use Authorization. However, even after this pandemic, COVID-19 may still have a chance to come back. Therefore, we need to come out with new strategies for drug discovery for combating COVID-19 in the future.

negative: Post-COVID-19 global health strategies: the need for an interdisciplinary approach For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

negative: Rhinosinusitis: Establishing definitions for clinical research and patient care Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Study design Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusions The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

negative: Antibiotic treatment for COVID-19 complications could fuel resistant bacteria In her regular job, Priya Nori runs Montefiore Medical Center’s antibiotic stewardship program, and spends most of her time ensuring that the Bronx-based hospital doesn’t overuse the drugs and allow bacteria resistant to them to thrive But like many physicians, Nori is now spending all of her time helping treat COVID-19 patients at her New York City hospital, which like other medical centers in the pandemic hot spot, is crowded with 50% more patients than normal As part of that care, she and other doctors are administering many more antibiotics than normal, which is a recipe for the rapid rise or spread of resistant bacteria, especially given the crowded conditions

negative: Estimate the incubation period of coronavirus 2019 (COVID-19) Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.

negative: Preventing COVID-19 and Its Sequela: “There Is No Magic Bullet . . . It's Just Behaviors”

negative: The challenges of COVID-19 for community pharmacists and opportunities for the future Pharmacists, like psychiatrists, have modified their practices amidst COVID-19 in order to guarantee care and support to their patients. Designated an essential frontline service, community pharmacists are facing a spectrum of challenges to surmount to ensure patient care continues. These include assisting in the prevention of infection, managing supply chains, preventing stockpiling and provision of evidence-based medical information. However, disasters like COVID-19 disproportionately affect poor and vulnerable populations, and patients with mental health conditions may be among the hardest hit. Pharmacist-level, system-level and regulatory responses have sought to minimise this impact, although there is likely to be a lasting impression on the profession, both good and bad. This article reviews the pandemic-related challenges and responses by pharmacists, as well as forming recommendation for areas of professional support and role expansion, particularly in the case of mental health.

negative: A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19) Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.

negative: Thermodynamic modeling of a novel air dehumidification system Abstract A novel air dehumidification system is proposed. The proposed system incorporates a membrane-based total heat exchanger into a mechanical air dehumidification system, where the fresh air flows through the enthalpy exchanger, the evaporator and the condenser subsequently. Thermodynamic model for the performance estimation of the combined system is investigated. Processes of the fresh air and the refrigerant are studied. Two additional specific programs are devised to calculate the psychrometrics and the thermodynamic properties of the refrigerant R134a. Annual energy requirement is 4.15 × 106 kJ per person, or 33% saving from a system without energy saving measures.

negative: Reactivation of SARS‐CoV‐2 after Recovery Coronavirus disease 2019 (COVID‐19) has now spread worldwide as a global pandemic.(1) We report on an 8‐year‐old boy who might be a patient with reactivation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a family cluster.

negative: Concepts of Security Threats, Challenges, Vulnerabilities and Risks The reconceptualization of security has been triggered by the end of the Cold War, by the process of globalization, and by the gradual transition from the Holocene to the Anthropocene phase of earth history (Brauch 2008, 2009, chap. 1 by Brauch/Oswald Spring above). From a philosophical perspective, in the contemporary security discussion the “dual moment of prevention and compensation of genuinely social and technical uncertainties” (Makropoulos 1995: 745–750) becomes decisive.

negative: Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19 BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has threaten the global health. The characteristics of laboratory findings of coronavirus are of great significance for clinical diagnosis and treatment. We found indicators that may most effectively predict a non-severe COVID-19 patient develop into a severe patient. METHODS: We conducted a meta-analysis to compare the laboratory findings of severe patients with non-severe patients with COVID-19 from searched articles. RESULTS: Through the analysis of laboratory examination information of patients with COVID-19 from 35 articles (5912 patients), we demonstrated that severe cases possessed higher levels of leukocyte (1.20-fold), neutrophil (1.33-fold), CRP (3.04-fold), PCT (2.00-fold), ESR (1.44-fold), AST (1.40-fold), ALT (1.34-fold), LDH (1.54-fold), CK (1.44-fold), CK-MB (1.39-fold), total bilirubin(1.14-fold), urea (1.28-fold), creatine (1.09-fold), PT (1.03-fold) and D-dimer (2.74-fold), as well as lower levels of lymphocytes (1.44-fold), eosinophil (2.00-fold), monocyte (1.08-fold), Hemoglobin (1.53-fold), PLT (1.15-fold), albumin (1.15-fold), and APTT (1.02-fold). Lymphocyte subsets and series of inflammatory cytokines were also different in severe cases with the non-severe ones, including lower levels of CD4 T cells (2.10-fold) and CD8 T cells (2.00-fold), higher levels of IL-1β (1.02-fold), IL-6 (1.93-fold) and IL-10 (1.55-fold). CONCLUSIONS: Some certain laboratory inspections could predict the progress of the COVID-19 changes, especially lymphocytes, CRP, PCT, ALT, AST, LDH, D-dimer, CD4 T cells and IL6, which provide valuable signals for preventing the deterioration of the disease.

negative: Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

negative: All eyes on Coronavirus—What do we need to know as ophthalmologists

negative: Socio-Economic Impacts of COVID-19 on Household Consumption and Poverty The COVID-19 pandemic has caused a massive economic shock across the world due to business interruptions and shutdowns from social-distancing measures. To evaluate the socio-economic impact of COVID-19 on individuals, a micro-economic model is developed to estimate the direct impact of distancing on household income, savings, consumption, and poverty. The model assumes two periods: a crisis period during which some individuals experience a drop in income and can use their precautionary savings to maintain consumption; and a recovery period, when households save to replenish their depleted savings to pre-crisis level. The San Francisco Bay Area is used as a case study, and the impacts of a lockdown are quantified, accounting for the effects of unemployment insurance (UI) and the CARES Act federal stimulus. Assuming a shelter-in-place period of three months, the poverty rate would temporarily increase from 17.1% to 25.9% in the Bay Area in the absence of social protection, and the lowest income earners would suffer the most in relative terms. If fully implemented, the combination of UI and CARES could keep the increase in poverty close to zero, and reduce the average recovery time, for individuals who suffer an income loss, from 11.8 to 6.7 months. However, the severity of the economic impact is spatially heterogeneous, and certain communities are more affected than the average and could take more than a year to recover. Overall, this model is a first step in quantifying the household-level impacts of COVID-19 at a regional scale. This study can be extended to explore the impact of indirect macroeconomic effects, the role of uncertainty in households' decision-making and the potential effect of simultaneous exogenous shocks (e.g., natural disasters).

negative: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.

negative: COVID-19 Pandemic and Surgical Oncology: Preserving the Academic Mission BACKGROUND: The global pandemic of respiratory disease cause by the novel human coronavirus (SARS-CoV-2) has caused untold suffering, loss of life and upheaval in society. The pandemic has lead to massive redirection of health care resources to treat the surge of COVID-19 patients, and enforcement of social distancing to reduce the rate of transmission. METHODS: Editorial Board members provided observations of the implications of the pandemic on academic surgical oncology. RESULTS: Delivery of health care to other populations including cancer patients has been significantly disrupted. The implications both short term and long term threaten preservation of the academic mission in medicine at large, and certainly in the field of surgical oncology. CONCLUSIONS: The effects on surgical oncology training, research and clinical trials are major.

negative: Epidemiological and Clinical Aspects of COVID-19; a Narrative Review There are significant misconceptions and many obstacles in the way of illuminating the epidemiological and clinical aspects of COVID-19 as a new emerging epidemic. In addition, usefulness of some evidence published in the context of the recent epidemic for decision making in clinic as well as public health is questionable. However, misinterpreting or ignoring strong evidence in clinical practice and public health probably results in less effective and somehow more harmful decisions for individuals as well as subgroups in general populations of countries in the initial stages of this epidemic. Accordingly, our narrative review appraised epidemiological and clinical aspects of the disease including genetic diversity of coronavirus genus, mode of transmission, incubation period, infectivity, pathogenicity, virulence, immunogenicity, diagnosis, surveillance, clinical case management and also successful measures for preventing its spread in some communities.

negative: Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

negative: Therapeutic Management of COVID-19 Patients: A systematic review Background: SARS-CoV-2 is the cause of the COVID-19 that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19. Aims of the study: this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus. Methods: A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed full articles in English published from December 1 st , 2019 to March 26 th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral, antibacterial. There were no restrictions on the type of study design eligible for inclusion. Results: As of March 26, 2020, of the initial manuscripts identified (n=449) articles. Forty-one studies were included, of which clinical trials (n=3), (case reports n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%). The most common mentioned and reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and oseltamivir (n=16). Conclusions: This is the first systematic review up to date related to the therapeutics used in COVID-19 patients. Only forty-one research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, corticosteroid therapy was found to be the most used medicine in these studies.

negative: Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review In a search to find effective treatments for COVID-19, chloroquine and hydroxychloroquine have gained attention. We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.

negative: Rapid AI Development Cycle for the Coronavirus (COVID-19) Pandemic: Initial Results for Automated Detection&Patient Monitoring using Deep Learning CT Image Analysis Purpose: Develop AI-based automated CT image analysis tools for detection, quantification, and tracking of Coronavirus; demonstrate they can differentiate coronavirus patients from non-patients. Materials and Methods: Multiple international datasets, including from Chinese disease-infected areas were included. We present a system that utilizes robust 2D and 3D deep learning models, modifying and adapting existing AI models and combining them with clinical understanding. We conducted multiple retrospective experiments to analyze the performance of the system in the detection of suspected COVID-19 thoracic CT features and to evaluate evolution of the disease in each patient over time using a 3D volume review, generating a Corona score. The study includes a testing set of 157 international patients (China and U.S). Results: Classification results for Coronavirus vs Non-coronavirus cases per thoracic CT studies were 0.996 AUC (95%CI: 0.989-1.00) ; on datasets of Chinese control and infected patients. Possible working point: 98.2% sensitivity, 92.2% specificity. For time analysis of Coronavirus patients, the system output enables quantitative measurements for smaller opacities (volume, diameter) and visualization of the larger opacities in a slice-based heat map or a 3D volume display. Our suggested Corona score measures the progression of disease over time. Conclusion: This initial study, which is currently being expanded to a larger population, demonstrated that rapidly developed AI-based image analysis can achieve high accuracy in detection of Coronavirus as well as quantification and tracking of disease burden.

negative: Rhinosinusitis: Establishing definitions for clinical research and patient care BACKGROUND: There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. OBJECTIVES: To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. METHODS: Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. RESULTS: Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. CONCLUSION: The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

negative: Should anti-diabetic medications be reconsidered amid COVID-19 pandemic?

negative: Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia BACKGROUND: Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. PURPOSE: To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. MATERIALS AND METHODS: This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. RESULTS: Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. CONCLUSION: In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.

negative: Clinical Research and Trials—A “Nonessential” Victim of the COVID-19 Pandemic?

negative: Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19 Background: Coronavirus disease 2019 (COVID-19) is the systemic entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may cause death through severe atypical pneumonia and acute lung injury. Valproic acid (VPA) has shown anti-inflammatory activity and mild intrinsic antiviral effect. These properties warrant the study of VPA as a possible active treatment in persons with severe COVID-19. Methods: Consecutive adult patients needing invasive mechanical ventilation (IMV) will be given intravenous (i.v.) VPA at a starting dose of 20 mg/kg/day and up to 60/kg/day (in 60 min i.v. infusions in 250 mL normal saline) as needed to reach plasma VPA concentrations of 50-100 mcg/mL (measured every 72 h). These patients will be followed-up for 10 days for the primary outcome and for a further period of 30 days after treatment completion for the secondary outcome of recurrence. The primary study outcome is the reduction in the case fatality rate of at least 50% after 10 days of treatment (as compared with natural history). Secondary outcomes are the reduction of length of stay (LOS) of at least 50%, as well as COVID-19 recurrence at 30-day follow-up. The most important safety outcomes are acute liver failure, acute pancreatitis, and thrombocytopenia. Conclusion: Although long-term adverse effects and even pro-inflammatory consequences have been reported with the chronic use of VPA, given the urgent need for a drug against COVID-19 to shorten the high mortality and LOS, the study of VPA is justified from a scientific standpoint.

negative: Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic Abstract The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD) have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become host or vectors of virus transmission. We hereby review the peer-reviewed and preprint literature pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.

negative: Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis.

negative: Bailout Strategies and Complications Associated with the Use of Flow-Diverting Stents for Treating Intracranial Aneurysms. Background Flow-diverting stents (FDS) have revolutionized the endovascular management of unruptured, complex, wide-necked, and giant aneurysms. There is no consensus on management of complications associated with the placement of these devices. This review focuses on the management of complications of FDS for the treatment of intracranial aneurysms. Summary We performed a systematic, qualitative review using electronic databases MEDLINE and Google Scholar. Complications of FDS placement generally occur during the perioperative period. Key Message Complications associated with FDS may be divided into periprocedural complications, immediate postprocedural complications, and delayed complications. We sought to review these complications and novel management strategies that have been reported in the literature.

negative: Flattening the Disability Curve: Rehabilitation and Recovery after COVID-19 Infection

negative: Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID ‐19 infected patients COVID‐19 pandemic is an emerging new human disease, where no vaccines, or monoclonal antibodies (mAbs), or drugs are currently available for therapy. Active vaccination requires the induction of an immune response against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease and this usually takes time to develop. Thus, the use of existing autologous Ab administration, obtainable from recovered COVID 19 patients, after 2 weeks recovery, is the best and the most practical strategy for providing immediate passive immunity to susceptible recipients in need.

negative: Survivors of COVID-19 are at high risk of posttraumatic stress disorder Posttraumatic stress disorder (PTSD) is a common mental disorder caused by major psychological trauma. It could result in serious distress and disability. Previous epidemic studies report high prevalence rates among people exposed to the trauma resulted from an infectious disease epidemic. While the control of the epidemic and care of patients with COVID-19 are still the dominant task of the whole world, this commentary calls for attention to early intervention and prevention of PTSD among huge numbers of COVID-19 survivors, their family members, health care professionals and other first-line helpers.

negative: Ensuring mental health care during the SARS-CoV-2 epidemic in France: a narrative review Abstract Objective: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. Methods: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. Results: We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: 1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; 2) age (the elderly form the population most vulnerable to the coronavirus); 3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and 4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist / infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. Discussion: French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.

negative: A blueprint for recovery for the postcoronavirus (COVID‐19) world Novel coronavirus (COVID-19) is changing society. In the last several weeks, infections and deaths have accumulated, even as we attempt to 'shelter in place' and stay 'healthy at home'. This unprecedented time has influenced behavior and permitted much contemplation, gratitude and prayer. Our thoughts during this time have focused on our emergence from the pandemic and what reopening may look like in the post-coronavirus world. Reopening will benefit from the acronym "RPM", an acronym I (CSM) teach my students for management of dental patients who suffer from a variety of illnesses and infections. Here, the 'R" stands for risk assessment and reduction, the first step in the sequence. The 'P' stands for prevention, and 'M' stands for manage the problem. If 'R' and 'P' are well conceived and implemented, often there is no need to apply 'M'.

negative: A review of the safety of favipiravir – a potential treatment in the COVID-19 pandemic? BACKGROUND: Repurposing broad-spectrum antivirals is an immediate treatment opportunity for 2019 coronavirus disease (COVID-19). Favipiravir is an antiviral previously indicated for influenza and Ebola, which has shown some promise in early trials for treatment of COVID-19. We aim to review existing favipiravir safety evidence, which is vital to informing the potential future use of favipiravir in COVID-19. METHODS: A search was conducted across EMBASE and MEDLINE databases, supplemented by relevant grey-literature and ClinicalTrials.gov. All studies assessing the use of favipiravir in humans by 27 March 2020 were considered for inclusion. Further analysis of available safety data from phase 2 and 3 studies was undertaken. Data extracted were adverse events (AEs) grade 1–4, serious AEs and discontinuation for AEs. Specific AEs of interest highlighted in early-phase studies, including gastrointestinal AEs and hyperuricaemia, were also examined. RESULTS: Twenty-nine studies were identified as potential sources of evidence of the clinical safety of favipiravir. Six were phase 2 and 3 studies reporting relevant safety data for statistical comparison, representing a total of 4299 participants, an estimated 175 person-years-of-follow-up (PYFU). Comparator drugs were oseltamivir, umifenovir, lopinavir/ritonavir or placebo. Study follow-up was between 5 and 21 days. The proportions of grade 1–4 AEs on favipiravir was 28.2% vs 28.4% (P = n.s.) in the comparison arms. The proportion of discontinuations due to AEs on favipiravir was 1.1% vs 1.2% (P = n.s.) in the comparison arms. For serious AEs the proportion was 0.4% in both arms (P = n.s.). There were significantly fewer gastrointestinal AEs occurring on favipiravir vs comparators [8.7% vs 11.5%; P = 0.003]. Favipiravir showed significantly more uric acid elevations than comparators [5.8% vs 1.3%; P<0.0001]. CONCLUSIONS: Favipiravir demonstrates a favourable safety profile regarding total and serious AEs. However, safety concerns remain: hyperuricaemia, teratogenicity and QTc prolongation have not yet been adequately studied. Favipiravir may be safe and tolerable in short-term use, but more evidence is needed to assess the longer-term effects of treatment. Given the limitations of the evidence and unresolved safety concerns, caution is warranted in the widespread use of favipiravir against pandemic COVID-19.

negative: Epidemiological features and medical care-seeking process of patients with COVID-19 in Wuhan, China BACKGROUND: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus. METHODS: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed. RESULTS: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection. CONCLUSIONS: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.

negative: Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection Objective To review and critically appraise published and preprint reports of models that aim to predict either (i) presence of existing COVID-19 infection, (ii) future complications in individuals already diagnosed with COVID-19, or (iii) models to identify individuals at high risk for COVID-19 in the general population. Design Rapid systematic review and critical appraisal of prediction models for diagnosis or prognosis of COVID-19 infection. Data sources PubMed, EMBASE via Ovid, Arxiv, medRxiv and bioRxiv until 24th March 2020. Study selection Studies that developed or validated a multivariable COVID-19 related prediction model. Two authors independently screened titles, abstracts and full text. Data extraction Data from included studies were extracted independently by at least two authors based on the CHARMS checklist, and risk of bias was assessed using PROBAST. Data were extracted on various domains including the participants, predictors, outcomes, data analysis, and prediction model performance. Results 2696 titles were screened. Of these, 27 studies describing 31 prediction models were included for data extraction and critical appraisal. We identified three models to predict hospital admission from pneumonia and other events (as a proxy for covid-19 pneumonia) in the general population; 18 diagnostic models to detect COVID-19 infection in symptomatic individuals (13 of which were machine learning utilising computed tomography (CT) results); and ten prognostic models for predicting mortality risk, progression to a severe state, or length of hospital stay. Only one of these studies used data on COVID-19 cases outside of China. Most reported predictors of presence of COVID-19 in suspected patients included age, body temperature, and signs and symptoms. Most reported predictors of severe prognosis in infected patients included age, sex, features derived from CT, C-reactive protein, lactic dehydrogenase, and lymphocyte count. Estimated C-index estimates for the prediction models ranged from 0.73 to 0.81 in those for the general population (reported for all 3 general population models), from 0.81 to > 0.99 in those for diagnosis (reported for 13 of the 18 diagnostic models), and from 0.85 to 0.98 in those for prognosis (reported for 6 of the 10 prognostic models). All studies were rated at high risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and poor statistical analysis, including high risk of model overfitting. Reporting quality varied substantially between studies. A description of the study population and intended use of the models was absent in almost all reports, and calibration of predictions was rarely assessed. Conclusion COVID-19 related prediction models are quickly entering the academic literature, to support medical decision making at a time where this is urgently needed. Our review indicates proposed models are poorly reported and at high risk of bias. Thus, their reported performance is likely optimistic and using them to support medical decision making is not advised. We call for immediate sharing of the individual participant data from COVID-19 studies to support collaborative efforts in building more rigorously developed prediction models and validating (evaluating) existing models. The aforementioned predictors identified in multiple included studies could be considered as candidate predictors for new models. We also stress the need to follow methodological guidance when developing and validating prediction models, as unreliable predictions may cause more harm than benefit when used to guide clinical decisions. Finally, studies should adhere to the TRIPOD statement to facilitate validating, appraising, advocating and clinically using the reported models. Systematic review registration protocol: osf.io/ehc47/, registration: osf.io/wy245

negative: Application of Enhanced Recovery After Surgery in Single-incision Laparoscopic Distal Gastrectomy. BACKGROUND Recently, enhanced recovery after surgery (ERAS) was widely used in the perioperative management of gastric cancer. The study aimed to evaluate the safety and effectiveness of ERAS in single-incision laparoscopic distal gastrectomy (SIDG). MATERIALS AND METHODS A total of 90 patients who received laparoscopic gastric cancer resection were divided into 3 groups: group A (n=30), underwent traditional multiport laparoscopic distal gastrectomy with conventional perioperative management; group B (n=30) underwent traditional multiport laparoscopic distal gastrectomy with ERAS concept; and group C (n=30), underwent SIDG with ERAS concept. Clinical data and gut function were assessed in 3 groups. RESULTS There were no significant differences in terms of postoperative complication, number of resected lymph nodes and blood loss among 3 groups. However, operation time was longer (P=0.003) and treatment cost was higher (P<0.001) in group C than that in group A and B. Group C had faster recovery of bowel function (P<0.001), shorter postoperative hospital stay (P=0.002), and less postoperative complication (P=0.044) than those in group A. There were no significant differences in terms of recovery of bowel function and postoperative hospital stay between group C and B (all P>0.05). The white blood cell counts were lower than group A and B (all P<0.05) and C-reactive protein in group C were lower than group A (P<0.05) and B (P>0.05). CONCLUSIONS The findings suggest that SIDG with ERAS may be a feasible and safe procedure for early gastric cancer because it provides a favorable cosmetic result while not compromising postoperative complications, number of resected lymph nodes, and blood loss.

negative: The experience on COVID-19 and cancer from an oncology hub institution in Milan, Lombardy Region Abstract The rapid outbreak of the SARS-CoV-2 related disease (COVID-19) has spread rapidly to a pandemic proportion, increasing the demands on health systems for the containment and management of COVID-19. Cancer has been reported as a major risk factor for adverse outcomes of and death from COVID-19. We extracted data from the World Health Organization’s progress reports and from the Italian Council of Medicine. In addition, we retrieved clinical data on cancer patients with confirmed COVID-19 in our Institution. As of April 2nd, 2020, 110 574 COVID-19 cases and 13 157 deaths have been described in Italy, representing a global share of 5.1% and 28.9% for incidence and mortality, respectively. In Italy, we report the analysis of the Italian Medical Council on 909 patients who died from COVID-19, of whom 16.5% were cancer patients. The population was enriched with subjects with multiple co-morbid non-communicable diseases, with less than 1% of the population presenting no co-morbid conditions. At the patient level, we identified nine patients referred to our department in the last two months who were receiving standard of care or experimental medications in the curative and palliative settings. The median age was 68 years (range: 42–79 years), and patients carried a median of one co-morbid condition (0–2); two out of nine patients presented with severe COVID-19 presentation, and were receiving inpatient care. None of the patients receiving immunotherapy experienced severe adverse outcomes, and four patients were discharged with complete reversal of the clinical syndrome and SARS-CoV-2 clearance. Learning from the experience of countries with a high burden, efforts must be made to assure the access of cancer patients to treatments, prioritizing the cancer health interventions based on their intrinsic value, and limiting the exposure to an unacceptable risk of infection for both health providers and patients. Any significant work in the design and implementation of health system actions, including in clinical care, must be framed as an initiative under the Global Response Agenda and through a community approach, with the intention of pursuing common goals to tackle COVID-19 and cancer, as ‘One Community’ working for ‘One Health’s.

negative: Les infections à coronavirus humains Résumé Les coronavirus humains (HCoV) sont des virus à ARN simple brin. Il existe actuellement quatre coronavirus dits « classiques » ou « nouveaux », dont la circulation est hivernale. Ils sont à l’origine d’infections respiratoires modérées dans la population générale. Cependant, les infections peuvent être plus sévères dans les populations susceptibles. Notamment, les HCoV sont impliqués dans 2 à 7% des hospitalisations consécutives à une infection respiratoire, en particulier chez les enfants et les personnes âgées ou immunodéprimées. De ce fait, ils appartiennent au panel de virus respiratoires recherchés lors des diagnostics de routine des infections respiratoires par des outils de biologie moléculaire. Ces coronavirus dits circulants sont à distinguer des deux coronavirus émergents, le SARS-CoV et le MERS-CoV qui sont associés à des pathologies respiratoires plus sévères. Ils se distinguent des autres HCoV par leur potentiel épidémique plus élevé, leur impact sanitaire plus important et leur mode de circulation atypique. À l’instar des paramyxovirus et des virus Influenza, les coronavirus doivent être surveillés pour leur risque d’émergence dans la population humaine à partir d’un réservoir animal. Summary Human coronaviruses (HCoV) are single strand RNA viruses. To date, there are four so-called « classical » or « novel » HCoVs, characterized by a winter circulation. These coronaviruses are responsible for mild respiratory infection in general population. However, HCoVs are associated to more severe respiratory tract infection among susceptible population. Indeed, HCoVs account for 2 to 7% of hospitalizations due to a respiratory infection, particularly among children, immunocompromised or elderly people. Thereby, HCoVs are included in the panel of respiratory viruses detected in routine using molecular biology tools. These four circulating HCoVs have to be distinguished from the two emerging HCoVs: SARS-CoV and MERS-CoV. These later are associated to a more severe respiratory infection and differ from other HCoVs by their increased epidemic potential, their more important health impact, and their atypical circulation. Such as paramyxoviruses and Influenza viruses, coronaviruses have to be monitored due to their associated risk of emergence in human population from animal reservoirs.

negative: T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV Abstract Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.

negative: Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients Objectives: Comorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. Methodology: We comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. Results: We found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. Conclusions: We conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.

negative: Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19) OBJECTIVES: To investigate the widely concerned issue about positive real-time reverse transcription polymerase chain reaction (RT-PCR) test results after discharge in patients recovered from coronavirus disease 2019 (COVID-19). METHODS: We identified seven cases of COVID-19 who was readmitted to hospital because of positive RT-PCR after discharge, including three pediatrics and four young adult patients. RESULTS: Six patients had positive rectal swabs but negative throat swabs, and one patient had positive throat swabs. All the patients continued to be asymptomatic and had unchanged chest computed tomography from previous images. The time from hospital discharge to positive RT-PCR after recovery was 7-11 days. The time from positive to negative rectal swabs was 5-23 days. CONCLUSION: The study might suggest the positive RT-PCR after recovery did not mean disease relapse or virus reinfection. Adding RT-PCR test of rectal swabs to the criteria for discharge or discontinuation of quarantine might be necessary.

negative: Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.

negative: Social Isolation as a predictor for mortality: Implications for COVID-19 prognosis The health benefits of social support have been widely documented. However, the social distancing practices from the COVID-19 pandemic is causing social disruption on a grand scale, potentially causing poor health outcomes. Through Google Trends analysis, we found a COVID-19-related surge in interest surrounding loneliness. We assessed if social isolation and loneliness increase the risk for all-cause and cardiovascular disease (CVD) mortality (ICD-10: I00-I99) and used the data to create a conceptual framework. Using the 10-year overall and cardiovascular mortality follow-up data (n = 12,019) from the National Health and Nutrition Examination Survey (1999-2008), we conducted survival analyses and found that individuals who experience social isolation or loneliness have a significantly higher likelihood of overall and CVD mortality than those without support. These effects generally remained strong with further adjustment for NHANES-detected health and demographic differences showing the need to address COVID-19 related loneliness through increasing social nearing.

negative: Scientific report on the effects of farming systems on dairy cow welfare and disease

negative: Clinical characteristics and chest CT imaging features of critically ill COVID-19 patients OBJECTIVES: To compare clinical, laboratory, and chest computed tomography (CT) findings in critically ill patients diagnosed with coronavirus disease 2019 (COVID-19) who survived and who died. METHODS: This retrospective study reviewed 60 critically ill patients (43 males and 17 females, mean age 64.4 ± 11.0 years) with COVID-19 pneumonia who were admitted to two different clinical centers. Their clinical and medical records were analyzed, and the chest CT images were assessed to determine the involvement of lobes and the distribution of lesions in the lungs between the patients who recovered from the illness and those who died. RESULTS: Compared with recovered patients (50/60, 83%), deceased patients (10/60, 17%) were older (mean age, 70.6 vs. 62.6 years, p = 0.044). C-reactive protein (CRP) (110.8 ± 26.3 mg/L vs 63.0 ± 50.4 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR) (18.7 ± 16.6 vs 8.4 ± 7.5, p = 0.030) were significantly elevated in the deceased as opposed to the recovered. Medial or parahilar area involvement was observed in all the deceased patients (10/10, 100%), when compared to only 54% (27/50) in the recovered. Ground-glass opacities (97%), crazy-paving pattern (92%), and air bronchogram (93%) were the most common radiological findings. There was significant difference in diabetes (p = 0.025) and emphysema (p = 0.013), and the odds ratio on a deceased patient having diabetes and emphysema was 6 times and 21 times the odds ratio on a recovered patient having diabetes and emphysema, respectively. CONCLUSIONS: Older patients with comorbidities such as diabetes and emphysema, and higher CRP and NLRs with diffuse lung involvement were more likely to die of COVID-19. KEY POINTS: • Almost all patients critically ill with COVID-19 pneumonia had five lung lobes involved. • Medial or parahilar area involvement and degree of lung involvement were more serious in the deceased patients when compared with those who recovered from treatment. • Chronic lung disease, e.g., emphysema, diabetes, and higher serum CRP and NLR characterized patients who died of COVID-19.

negative: Managing emerging infectious diseases: Is a federal system an impediment to effective laws? In the 1980's and 1990's HIV/AIDS was the emerging infectious disease. In 2003–2004 we saw the emergence of SARS, Avian influenza and Anthrax in a man made form used for bioterrorism. Emergency powers legislation in Australia is a patchwork of Commonwealth quarantine laws and State and Territory based emergency powers in public health legislation. It is time for a review of such legislation and time for consideration of the efficacy of such legislation from a country wide perspective in an age when we have to consider the possibility of mass outbreaks of communicable diseases which ignore jurisdictional boundaries.

negative: Effects of total fat intake on bodyweight in children. BACKGROUND As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES To assess the effects and associations of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective cohort studies if they related baseline total fat intake to weight or body fatness at least 12 months later. DATA COLLECTION AND ANALYSIS We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted body weight and blood lipid levels outcomes at six months, six to 12 months, one to two years, two to five years and more than five years for RCTs; and for cohort studies, at baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three studies were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous to combine.Effects of dietary counselling to reduce total fat intake from RCTsTwo studies recruited children aged between 4 and 11 years and a third recruited children aged 12 to 13 years. Interventions were combinations of individual and group counselling, and education sessions in clinics, schools and homes, delivered by dieticians, nutritionists, behaviourists or trained, supervised teachers. Concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability.One study of dietary counselling to lower total fat intake found that the intervention may make little or no difference to weight compared with usual diet at 12 months (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; n = 620; low-quality evidence) and at three years (MD -0.60 kg, 95% CI -2.39 to 1.19; n = 612; low-quality evidence). Education delivered as a classroom curriculum probably decreased BMI in children at 17 months (MD -1.5 kg/m2, 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence). The effects were smaller at longer term follow-up (five years: MD 0 kg/m2, 95% CI -0.63 to 0.63; n = 541; seven years; MD -0.10 kg/m2, 95% CI -0.75 to 0.55; n = 576; low-quality evidence).Dietary counselling probably slightly reduced total cholesterol at 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Dietary counselling probably slightly decreased low-density lipoprotein (LDL) cholesterol at 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and at five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. Dietary counselling probably made little or no difference to HDL-C at 12 months (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), and at five years (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, counselling probably made little or no difference to triglycerides in children at 12 months (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height at seven years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Associations between total fat intake, weight and body fatness from cohort studiesOver half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to dietary counselling or education to lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls. There were no consistent effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Most studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings to look at both possible benefits and harms.

negative: Role of phosphorylation clusters in the biology of the coronavirus infectious bronchitis virus nucleocapsid protein Abstract The coronavirus infectious bronchitis virus (IBV) nucleocapsid (N) protein is an RNA binding protein which is phosphorylated at two conserved clusters. Kinetic analysis of RNA binding indicated that the C-terminal phosphorylation cluster was involved in the recognition of viral RNA from non-viral RNA. The IBV N protein has been found to be essential for the successful recovery of IBV using reverse genetics systems. Rescue experiments indicated that phosphorylated N protein recovered infectious IBV more efficiently when compared to modified N proteins either partially or non-phosphorylated. Our data indicate that the phosphorylated form of the IBV N protein plays a role in virus biology.

negative: Smoking is Associated with COVID-19 Progression: A Meta-Analysis Objective: To determine the association between smoking and progression of COVID-19. Design: A meta-analysis of 12 published papers. Data Source: PubMed database was searched on April 6, 2020. Eligibility criteria and data analysis: We included studies reporting smoking behavior of COVID-19 patients and progression of disease. Search terms included smoking, smoker*, characteristics, risk factors, outcomes, and COVID-19, COVID, coronavirus, sar cov-2, sar cov 2. There were no language limitations. One author extracted information for each study, screened the abstract or the full text, with questions resolved through discussion among both authors. A random effects meta-analysis was applied. Main Outcome Measures: The study outcome was progression of COVID-19 among people who already had the disease. Results: We identified 12 papers with a total of 9,025 COVID-19 patients, 878 (9.7%) with severe disease and 495 with a history of smoking (5.5%). The meta-analysis showed a significant association between smoking and progression of COVID-19 (OR 2.25, 95% CI 1.49-3.39, p=0.001). Limitations in the 12 papers suggest that the actual risk of smoking may be higher. Conclusions: Smoking is a risk factor for progression of COVID-19, with smokers having higher odds of COVID-19 progression than never smokers. Physicians and public health professionals should collect data on smoking as part of clinical management and add smoking cessation to the list of practices to blunt the COVID-19 pandemic.

negative: Genetic inactivation of COPI coatomer separately inhibits vesicular stomatitis virus entry and gene expression. Viruses coopt cellular membrane transport to invade cells, establish intracellular sites of replication, and release progeny virions. Recent genome-wide RNA interference (RNAi) screens revealed that genetically divergent viruses require biosynthetic membrane transport by the COPI coatomer complex for efficient replication. Here we found that disrupting COPI function by RNAi inhibited an early stage of vesicular stomatitis virus (VSV) replication. To dissect which replication stage(s) was affected by coatomer inactivation, we used visual and biochemical assays to independently measure the efficiency of viral entry and gene expression in hamster (ldlF) cells depleted of the temperature-sensitive ε-COP subunit. We show that ε-COP depletion for 12 h caused a primary block to virus internalization and a secondary defect in viral gene expression. Using brefeldin A (BFA), a chemical inhibitor of COPI function, we demonstrate that short-term (1-h) BFA treatments inhibit VSV gene expression, while only long-term (12-h) treatments block virus entry. We conclude that prolonged coatomer inactivation perturbs cellular endocytic transport and thereby indirectly impairs VSV entry. Our results offer an explanation of why COPI coatomer is frequently identified in screens for cellular factors that support cell invasion by microbial pathogens.

negative: Longitudinal analysis of laboratory findings during the process of recovery for patients with COVID-19 Objective To explore longitudinal change patterns of key laboratory tests in patients with COVID-19, and to identify independent prognostic factors by examining the associations between laboratory findings and outcomes of patients. Methods The multicenter study prospectively included 59 patients with COVID-19 treated at Jilin province from January 21, 2020 to May 5, 2020. Laboratory tests were included haematological, biochemical, and immunological tests. Results Laboratory findings, the characteristics of epidemiological and demographic data were extracted from electronic medical records. Eosinopenia was shown in 52.6% cases at onset, and the average value of eosinophil continued to significantly increase thereafter. Lymphopenia was found in 40.4% cases at onset, and the average value of lymphocyte was slowly elevated after day 5. Thrombocytopenia was shown in 12.3% cases at onset, and the average value of mean platelet volume was decreased sharply after day 7. The values of aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatinine kinase-muscle/brain activity, and cardiac troponin I, serum cardiac markers, were beyond the upper limit of RI from 6.1% to 30.6% at onset. The abnormity of liver function tests, kidney function tests, electrolytes was 2.0%~59.2%, 2.0%~4.1%, 6.0%~30.0%, respectively. Eosinophil, platelet and carbondioxide combining power were selected as the prognostic factors. Conclusions The haematological, biochemical, and immunological tests were found significant abnormity at onset and longitudinal change patterns in the patients with COVID-19. Age, Eosinophil, PLT and CO2 may used to predict the recovery probability. Risk stratification and management could be improved for the patients with COVID-19 according to temporal trajectories of laboratory tests.

negative: Effects of latency on estimates of the COVID-19 replication number It is not currently known how long it takes a person infected by the COVID-19 virus to become infectious. Models of the spread of COVID-19 use very different lengths for this latency period, leading to very different estimates of the replication number R, even when models work from the same underlying data sets. In this paper we quantify how much varying the length of the latency period affects estimates of R, and thus the fraction of the population that is predicted to be infected in the first wave of the pandemic. This variation underscores the uncertainty in our understanding of R and raises the possibility that R may be considerably greater than has been assumed by those shaping public policy.

negative: Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection. BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries' mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials.

negative: Recomendaciones de “hacer” y “no hacer” en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)◊ Abstract On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.

negative: The diagnostic value of detecting sudden smell loss among asymptomatic COVID-19 patients in early stage: The possible early sign of COVID-19 IMPORTANCE: The newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function. OBSERVATIONS: Rapid reviews for COVID-19 or other viral infection and olfactory and/or gustatory dysfunctions were done in this review. Up to date, a lot of reports have shown that olfactory dysfunction is related to viral infections but no exact mechanism, clinical course, and definite treatment have been discovered, which is also same in COVID-19. In general, intranasal steroid (INS) and oral steroid for short time help improve the recovery of the olfactory function in case of olfactory dysfunction after virus infection. Considering severe respiratory complications and immunocompromised state of COVID-19, the use of steroid should be limited and cautious because we do not have enough data to support the usage of steroid to treat olfactory dysfunction in the clinical course of COVID-19. CONCLUSIONS AND RELEVANCE: In the days of pandemic COVID-19, we should keep in mind that olfactory dysfunctions, even without other upper respiratory infection or otolaryngologic symptoms, might be the early signs of COVID-19.

negative: Chinese experts’ consensus on the Internet of Things-aided diagnosis and treatment of coronavirus disease 2019 (COVID-19) Abstract The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

negative: Clinical Characteristics and Outcomes of 421 Patients with COVID-19 Treated in a Mobile Cabin Hospital Abstract Background In December 2019, a novel coronavirus-associated pneumonia (COVID-19) was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. Research Question Whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms remains unknown. Study Design and Methods We retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9th to March 5th, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. Results The outcome was recovery and hospital discharge in 86% of patients, while 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%), while 5.2% showed no obvious symptoms. High fever (>39.0°C) was more common in severe cases than recovered cases (18.6% versus 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in severe patients (66.1%) than in those who recovered (31.8%, P<.0001). The median length of hospitalization was 17 (14–19) days, and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 (6–10) days. Interpretation Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms, and provide an effective isolation area to prevent the spread of SARS-CoV-2.

negative: The impact of coronavirus infectious disease 19 (COVID‐19) on oral health Health services across the world face an unprecedented situation as a result of a global COVID‐19 outbreak. Urgent joined research efforts regarding the SARS‐COV‐2 rapid tests, accurate diagnosis, especially early recognition, and effective treatment of life‐threatening complications would be highly desirable for humanity and medical workforce all over the world that try to combat a current global pandemic threat. Due to indirect complex effect, intensified COVID‐19 therapies and multi‐drug treatment, it is believed that some oral conditions could be aggravated by COVID‐19 disease, particularly those with autoimmune aetiology, linked to compromised immune system or long‐term pharmacotherapy.

negative: Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy Coronavirus disease 2019 (COVID-19) is a pandemic. Neurological complications of COVID-19 have not been reported. Encephalopathy has not been described as a presenting symptom or complication of COVID-19. We report a case of a 74-year-old patient who traveled from Europe to the United States and presented with encephalopathy and COVID-19.

negative: Two X‐linked agammaglobulinemia patients develop pneumonia as COVID‐19 manifestation but recover BACKGROUND: The recent SARS‐CoV‐2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease‐19 (COVID‐19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS‐CoV‐2. Therefore, we evaluated the outcome of SARS‐CoV‐2 infection in patients with inborn errors of immunity (IEI) such as X‐linked agammaglobulinemia (XLA). METHODS: When the SARS‐CoV‐2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS‐CoV‐2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID‐19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X‐linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID‐19, as diagnosed by SARS‐CoV‐2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS‐CoV‐2 infection, but can recover from infection, suggesting that B‐cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.

negative: Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study Summary Background In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. Methods In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed. Findings Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29–34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth. Interpretation The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature. Funding National Natural Science Foundation of China, Hubei Provincial Natural Science Foundation of China.

negative: Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia Salvage corticosteroids treatment for critical patients with 2019-nCoV? Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5. Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1). Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6,7,8. However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.

negative: Reproducibility and reporting practices in COVID-19 preprint manuscripts The novel coronavirus, COVID-19, has sparked an outflow of scientific research seeking to understand the virus, its spread, and best practices in prevention and treatment. If this international research effort is going to be as swift and effective as possible, it will need to rely on a principle of open science. When researchers share data, code, and software and generally make their work as transparent as possible, it allows other researchers to verify and expand upon their work. Furthermore, it allows public officials to make informed decisions. In this study, we analyzed 535 preprint articles related to COVID-19 for eight transparency criteria and recorded study location and funding information. We found that individual researchers have lined up to help during this crisis, quickly tackling important public health questions, often without funding or support from outside organizations. However, most authors could improve their data sharing and scientific reporting practices. The contrast between the commitment of researchers to doing important research and their reporting practices reveals underlying weaknesses in reporting habits, but not necessarily their science.

negative: Characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan, China Background Since Dec 2019, SARS-CoV-2 has caused about fifty thousand patients and over two thousand deaths in Wuhan, China. We reported characteristics of patients with COVID-19 during epidemic ongoing outbreak in Wuhan. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, were retrospectively collected from electronic medical records. Characteristics were compared between patients who died or recovered, and between patients with different disease severity. Results By Feb 25, 2020, 403 patients were enrolled, 100 died and 303 recovered. Most of non-survivors tended to be males, old aged, or with chronic diseases. Duration from illness onset to admission was 9 (7-12) days. Patients with severe or critical illness had more days from onset to admission compared to those with ordinary illness. Lymphopenia, anemia, hypoproteinemia, and abnormal serum sodium were presented in 52.6%, 54.6%, 69.8%, and 21.8% cases, respectively. Patients who died or with severe/critical illness showed increased white blood cell and neutrophil count, serum total bilirubin, creatinine, hypersensitive troponin I, D-dimer, procalcitonin, and C-reactive protein, and decreased red blood cell, lymphocyte, platelet count, and serum albumin on admission compared to those who recovered or with ordinary illness. Complications of acute organ injury and secondary infection were common in patients with COVID-19, especially in non-survivors. Conclusions Multiple homeostasis disturbances were common in patients with severe or critical illness at admission. Early support should be provided, especially for old men with chronic disease, which is vital to control disease progression and reduce mortality of COVID-19 during epidemic ongoing outbreak.

negative: Climate change and peak oil—two large-scale disruptions likely to adversely affect long-term tourism growth in the Asia Pacific Abstract Climate change and peak oil are likely to have a significant impact on future tourism growth in the Asia Pacific region. Dealing with these issues and the policies and strategies required for mitigation and adaptation need to be given far greater attention by the tourism industry and the public sector than has hitherto been the case. Existing approaches based on crisis and disaster management may be inadequate and a new approach to deal with shocks of this nature is required. This regional spotlight suggests a new approach based on the concept of disruption which is defined as an event that causes substantial and long-term change in the structure of the tourism industry.

negative: Maternal and perinatal outcomes with COVID‐19: A systematic review of 108 pregnancies INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID‐19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID‐19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS‐CoV‐2. Eligibility criteria included peer‐reviewed publications written in English or Chinese and quantitative real‐time polymerase chain reaction (PCR) or dual fluorescence PCR‐confirmed SARS‐CoV‐2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID‐19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C‐reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID‐19 and perinatal deaths were reported. Vertical transmission of the COVID‐19 could not be ruled out. Careful monitoring of pregnancies with COVID‐19 and measures to prevent neonatal infection are warranted.

negative: [Epidemiological characteristics of confirmed COVID-19 cases in Tianjin]. Objective: To investigate the clinical and epidemiological characteristics of 135 confirmed cases of COVID-19 in Tianjin. Methods: The clinical and epidemiological data of 135 cases of COVID-19 in Tianjin were collected, and the data were analyzed with descriptive method. The factors influencing the severity of the illness were analyzed. Results: Among the 135 COVID-19 cases, 72 were males and 63 were females, the age of the cases was (48.62±16.83) years, and the case fatality rate was 2.22%. Local transmission caused 74.81% of the cases. A total of 33 clusters occurred, involving 85.92% of all COVID-19 cases. The median of the incubation period of COVID-19 was 6.50 days, the average generation interval was 5 days, and the household secondary transmission rate was 20.46%. Fever was the main symptom (78.63%), followed by cough (56.48%). Multivariate regression analysis indicated that age (OR=1.038, 95%CI: 1.010-1.167) and the number of chronic underlying diseases (OR=1.709, 95%CI: 1.052-2.777) were the risk factors of severe illness. Conclusions: Fever was the main symptom at the early phase of COVID-19 in Tianjin, and the local cluster cases accounted for high proportion in confirmed COVID-19 cases reported in Tianjin. Severe illness was prone to occur in people with old age and multi underlying diseases. Strict isolation of close contacts and intensive care of high-risk groups are the main measures to reduce the morbidity and case fatality of COVID-19.

negative: Patient Follow-up after Discharge after COVID-19 Pneumonia: Considerations for Infectious Control Coronavirus disease 2019 (COVID-19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID-19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID-19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long-term pulmonary defects, and post-traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID-19 for reference to come to a consensus on follow-up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long-term follow-up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.

negative: Long-Term Neurological Threats of COVID-19: A Call to Update the Thinking About the Outcomes of the Coronavirus Pandemic

negative: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy Abstract Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.

negative: Need for ensuring care for neuro-emergencies-lessons learned from the COVID-19 pandemic BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.

negative: Priapism in a patient with coronavirus disease 2019 (COVID-19): A case report Thromboembolic complications related to SARS-CoV-2 have been extensively reported. They include deep vein thrombosis, pulmonary embolism, ischemic stroke, and acute coronary syndrome. Penile thrombosis has not been reported as a thrombotic complication of SARS-CoV-2 infection with hypercoagulability. Here we describe a case of priapism as a thromboembolic complication in a patient with COVID-19 who recovered from acute respiratory distress syndrome (ARDS). We discuss the underlying pathophysiological mechanisms mainly related to an hypercoagulability state. Emergency management consisted on an intracavernosal injection of the sympathomimetic agent ethylephrine and cavernosal blood aspiration. The patient experienced no recurrences under thromboprophylaxis by enoxaparin 40 mg twice daily.

negative: Protective and Therapeutic Effects of Licorice in Rats With Acute Tubular Necrosis Objectives Various protective and therapeutic effects such as antioxidant, anti-inflammatory, anticancer, antihistaminic, and antibacterial effects have been depicted for licorice. However, its biological effects in the kidney are still not clear. Therefore, we aimed to investigate the efficiency of licorice in rats with gentamicin (GM)-induced acute tubular necrosis. Design and Methods Rats were randomized into the control group (only saline for 12 days), licorice group (licorice for 12 days), GM group (GM for 12 days), GM + licorice group, and licorice-treated GM group (licorice for 12 days after taking GM for 12 days). Blood urea, creatinine, and uric acid levels were measured and histopathological analyses of the kidneys were performed. The oxidative side of oxidant-antioxidant balance was evaluated by detecting lipid peroxidation (LPO) and total peroxide levels, and antioxidative side was determined by measuring total antioxidant capacity (TAC) and reduced glutathione (GSH) levels in plasma and kidney tissues. Results The oxidant-antioxidant balance seemed to be shifted to the oxidative side in the GM group when compared with the control and GM + licorice groups. In GM group, biochemical profiles showed a remarkable increase in blood uric acid, urea, and creatinine levels, and depletion of renal tissue and plasma TAC and GSH levels. In addition, histopathologic studies revealed severe acute tubular necrosis, congestion, and hyaline casts, verifying GM-induced nephrotoxicity. Licorice was effective in reduction of blood urea, creatinine, and uric acid levels, and also effective in decreasing the tubular necrosis score. Licorice treatment also significantly reduced LPO and total peroxide levels, and increased TAC and GSH levels in both renal tissue and blood. Moreover, these changes in rats subjected to the combined therapy (GM + licorice) were significantly less than those of GM group. Conclusions Licorice ameliorates GM-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing LPO, and improving antioxidant defense.

negative: Clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) patients Background: Numerous groups have reported the clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) cases; however, the data remained inconsistent. This paper aimed to pool the available data to provide a more complete picture of the characteristics of COVID-19 patients. Methods: A systematic review and pooled analysis was performed. Eligible studies were identified from database and hand searches up to March 2, 2020. Data on clinical (including laboratory and radiological) and epidemiological (including demographic) characteristics of confirmed COVID-19 cases were extracted and combined by simple pooling. Results: Of 644 studies identified, 69 studies (involving 48,926 patients) were included in the analysis. The average age of the patients was 49.16 years. A total of 51.46% of the patients were men and 52.32% were non-smokers. Hypertension (50.82%) and diabetes (20.89%) were the most frequent comorbidities observed. The most common symptoms were fever (83.21%), cough (61.74%), and myalgia or fatigue (30.22%). Altered levels of blood and biochemical parameters were observed in a proportion of the patients. Most of the patients (78.50%) had bilateral lung involvements, and 5.86% showed no CT findings indicative of viral pneumonia. Acute respiratory distress syndrome (28.36%), acute cardiac injury (7.89%) and acute kidney injury (7.60%) were the most common complications recorded. Conclusions: Clinical and epidemiological characteristics of COVID-19 patients were mostly heterogeneous and non-specific. This is the most comprehensive report of the characteristics of COVID-19 patients to date. The information presented is important for improving our understanding of the spectrum and impact of this novel disease.

negative: Advances in the Relationship Between Coronavirus Infection and Cardiovascular Diseases The outbreak of coronavirus disease 2019 (COVID-19) has once again aroused people's concern about coronavirus. Seven human coronaviruses (HCoVs) have been discovered so far, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU115, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. Existing studies show that the cardiovascular disease increased the incidence and severity of coronavirus infection. At the same time, myocardial injury caused by coronavirus infection is one of the main factors contributing to poor prognosis. In this review, the recent clinical findings about the relationship between coronaviruses and cardiovascular diseases and the underlying pathophysiological mechanisms are discussed. This review aimed to provide assistance for the prevention and treatment of COVID-19.

negative: The production of antibodies for SARS-CoV-2 and its clinical implication Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.

negative: Cardiac and arrhythmic complications in patients with COVID‐19 In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.

negative: Coronavirus drugs: Using plasma from recovered patients as a treatment for COVID-19 The ongoing COVID-19 pandemic has infected nearly 3,582,233 individuals with 248,558 deaths since it was first identified in human populations in December 2019 in Wuhan, China. No antiviral therapies or vaccines are available for their treatment or prevention. Passive immunization PI through broadly neutralizing antibodies that bind to the specific antigens of SARS-CoV 2 might be a potential solution to address the immediate health threat of COVID-19 pandemic while vaccines are being developed. The PI approach in treating COVID-19 is discussed herein, including a summary of its historical applications to confront epidemics.

negative: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. Importance There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/minute, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. Mortality for those requiring mechanical ventilation was 88.1%. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

negative: The explosive epidemic outbreak of novel coronavirus disease 2019 (COVID-19) and the persistent threat of respiratory tract infectious diseases to global health security

negative: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.

negative: Co-stimulation: novel methods for preventing viral-induced lung inflammation Respiratory infections cause significant morbidity and mortality worldwide. Although an immune response is required to eliminate respiratory pathogens, if unchecked, it can damage surrounding tissues and block primary lung function. Based on our knowledge of immune T-cell activation, there are several pathways to which immune intervention could be applied. However, relatively few interventions target only those immune cells that are responding to antigens. OX40 and 4-1BB are members of the tumour necrosis factor receptor family and are expressed on the surface of T cells in several inflammatory conditions. Recently, the inhibition of OX40 has proved beneficial during influenza virus infection. This review highlights the recent advances in the manipulation of such molecules and how they have been applied to inflammatory conditions that are caused by viruses in the lung.

negative: Association between Initial Chest CT or Clinical Features and Clinical Course in Patients with Coronavirus Disease 2019 Pneumonia OBJECTIVE: To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values < 1 indicated a lower rate of discharge at four weeks and longer time until discharge. RESULTS: Thirty-two patients recovered and were discharged during the study period with a median length of admission of 16 days (range, 9 to 25 days), while the rest remained hospitalized at the end of this study (median, 17.5 days; range, 4 to 27 days). None died during the study period. After controlling for age, onset time, lesion characteristics, number of lung lobes affected, and bilateral involvement, the lung severity score on baseline CT (> 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18-0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03-0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. CONCLUSION: Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.

negative: Liver diseases in COVID-19: Etiology, treatment and prognosis In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China causing coronavirus disease-2019 (COVID-19). Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2. However, in previous case studies of COVID-19, the exact cause of liver injury has not been clearly elucidated, nor is there clear evidence of the interaction between liver injury and COVID-19. This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.

negative: A systematic review of convalescent plasma treatment for COVID19 Background. Transfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease. Methods. A systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature. Results. From 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment. Conclusions. Limited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, reveal no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.

negative: Failed detection of the full-length genome of SARS-CoV-2 by ultra-deep sequencing from the recovered and discharged patients retested viral PCR positive Over 10 percent of recovered and discharged patients retested positive for SARS-CoV-2, raising a public health concern whether they could be potential origins of infection. In this study, we found that detectable viral genome in discharged patients might only mean the presence of viral fragments, and could hardly form an infection origin for its extremely low concentration.

negative: COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy

negative: V-, U-, L-, or W-shaped recovery after COVID? Insights from an Agent Based Model We discuss the impact of a Covid-like shock on a simple toy economy, described by the Mark-0 Agent-Based Model that we developed and discussed in a series of previous papers. We consider a mixed supply and demand shock, and show that depending on the shock parameters (amplitude and duration), our toy economy can display V-shaped, U-shaped or W-shaped recoveries, and even an L-shaped output curve with permanent output loss. This is due to the existence of a self-sustained"bad"state of the economy. We then discuss two policies that attempt to moderate the impact of the shock: giving easy credit to firms, and the so-called helicopter money, i.e. injecting new money into the households savings. We find that both policies are effective if strong enough, and we highlight the potential danger of terminating these policies too early. While we only discuss a limited number of scenarios, our model is flexible and versatile enough to allow for a much wider exploration, thus serving as a useful tool for the qualitative understanding of post-Covid recovery. We provide an on-line version of the code at https://gitlab.com/sharma.dhruv/markovid .

negative: COVID-19: Four Paediatric Cases in Malaysia Abstract Objective This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia Background COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. Cases In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. Discussion There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

negative: Updated understanding of the outbreak of 2019 novel coronavirus (2019‐nCoV) in Wuhan, China To help health workers and the public recognize and deal with the 2019 novel coronavirus (2019‐nCoV) quickly, effectively, and calmly with an updated understanding. A comprehensive search from Chinese and worldwide official websites and announcements was performed between 1 December 2019 and 9:30 am 26 January 2020 (Beijing time). A latest summary of 2019‐nCoV and the current outbreak was drawn. Up to 24 pm, 25 January 2020, a total of 1975 cases of 2019‐nCoV infection were confirmed in mainland China with a total of 56 deaths having occurred. The latest mortality was approximately 2.84% with a total of 2684 cases still suspected. The China National Health Commission reported the details of the first 17 deaths up to 24 pm, 22 January 2020. The deaths included 13 males and 4 females. The median age of the people who died was 75 (range 48‐89) years. Fever (64.7%) and cough (52.9%) were the most common first symptoms among those who died. The median number of days from the occurence of the first symptom to death was 14.0 (range 6‐41) days, and it tended to be shorter among people aged 70 years or more (11.5 [range 6‐19] days) than those aged less than 70 years (20 [range 10‐41] days; P = .033). The 2019‐nCoV infection is spreading and its incidence is increasing nationwide. The first deaths occurred mostly in elderly people, among whom the disease might progress faster. The public should still be cautious in dealing with the virus and pay more attention to protecting the elderly people from the virus.

negative: A complication of coronavirus disease 2019: delirium COVID-19 is predominantly a respiratory disease. However, some cases exhibit other features including Central Nervous System symptoms. In the older adult, COVID-19 may present with atypical symptoms, including delirium and its complications. The objective of this study is to describe the relationship between the new type of coronavirus infection and delirium. Systematic research (Cochrane Library and PubMed) was carried out (only upper time limit: April 2020). Publications found through this indexed search were reviewed and manually screened to identify relevant studies. Search terms used included "COVID-19, Delirium, Dementia, Intensive Care Unit". We manually added articles identified through other sources (i.e., key journals). Older people are at the greatest risk from COVID-19. If infected, they may present delirium. Moreover, it is not exclusive to older people. Delirium is not inevitable; rather, it is preventable. Delirium prevention programs are even more crucial in the era of COVID-19 and cannot be allowed to wither despite the challenges of integrating delirium prevention with COVID-19 care. An acute change in condition, behaviour, or mental status should prompt a delirium screen. As regards the treatment, it is advisable to use non-pharmacological interventions first where possible. Medication may be needed for patients with agitation where there is intractable distress or high risk to self/others.

negative: Hydroxychloroquine alone or in combination with azithromycin to prevent major clinical events in hospitalised patients with coronavirus infection (COVID-19): rationale and design of a randomised, controlled clinical trial Introduction: Hydroxychloroquine and its combination with azithromycin have been suggested to improve viral clearance in patients with COVID-19, but its effect on clinical outcomes remains uncertain. Methods and analysis: We describe the rationale and design of an open-label pragmatic multicentre randomised (concealed) clinical trial of 7 days of hydroxychloroquine (400 mg BID) plus azithromycin (500 mg once daily), hydroxychloroquine 400 mg BID, or standard of care for moderately severe hospitalised patients with suspected or confirmed COVID-19 (in-patients with up to 4L/minute oxygen supply through nasal catheter). Patients are randomised in around 50 recruiting sites and we plan to enrol 630 patients with COVID-19. The primary endpoint is a 7-level ordinal scale measured at 15-days: 1)not hospitalised, without limitations on activities; 2)not hospitalised, with limitations on activities; 3)hospitalised, not using supplementary oxygen; 4)hospitalised, using supplementary oxygen; 5)hospitalised, using high-flow nasal cannula or non-invasive ventilation; 6)hospitalised, on mechanical ventilation; 7)death. Secondary endpoints are the ordinal scale at 7 days, need for mechanical ventilation and rescue therapies during 15 days, need of high-flow nasal cannula or non-invasive ventilation during 15 days, length of hospital stay, in-hospital mortality, thromboembolic events, occurrence of acute kidney injury, and number of days free of respiratory support at 15 days. Secondary safety outcomes include prolongation of QT interval on electrocardiogram, ventricular arrhythmias, and liver toxicity. The main analysis will consider all patients with confirmed COVID-19 in the groups they were randomly assigned. Ethics and dissemination: This study has been approved by Brazil's National Ethic Committee (CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete, as well as presented and reported to local health agencies. ClinicalTrials.gov identifier: NCT04322123

negative: The 1-Year Impact of Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity, and Quality of Life in a Cohort of Survivors Objective To examine pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among severe acute respiratory syndrome (SARS) survivors. Methods We evaluated survivors with confirmed SARS at the Prince of Wales Hospital, Hong Kong, at 3, 6, and 12 months after symptom onset. Our assessment included: lung volume (total lung capacity [TLC], vital capacity, residual volume, functional residual capacity), spirometry (FVC, FEV1), diffusing capacity of the lung for carbon monoxide (Dlco), inspiratory and expiratory respiratory muscle strength, 6-min walk distance (6MWD), chest radiographs (CXRs), and HRQoL by Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire. Results Ninety-seven patients completed the serial assessments. There were 39 male and 58 female patients, and 63 patients (70%) were health-care workers (mean age, 36.9 years [SD, 9.5 years]; body mass index, 23.7 kg/m2 [SD, 4.0 kg/m2]). At 1 year, 27 patients (27.8%) had abnormal CXR findings. Four patients (4.1%), 5 patients (5.2%), and 23 patients (23.7%) had FVC, TLC, and Dlco values < 80% of predicted values, respectively. The 6MWD at 12 months was 511.0 m (SD, 89.8 m), which was higher than at 3 months (mean difference, 47.0 m; 95% confidence interval [CI], 31.8 to 62.1 m; p < 0.01) but not different from 6 months (mean difference, 9.7 m; 95% CI, − 4.4 to 23.8 m; p = 0.18). The 6MWD was lower than that for normal control subjects of the same age groups, and there was impairment of HRQoL at 12 months. Patients who required ICU admission (n = 31) showed higher CXR scores (1.6 [SD, 3.1]; vs 0.4 [SD, 1.1]; p = 0.04) and lower percentage of predicted FVC, TLC, and Dlco than those who did not, but there were no differences in 6MWD and health status. Conclusion Significant impairment in Dlco was noted in 23.7% of survivors 1 year after illness onset. Exercise capacity and health status of SARS survivors were remarkably lower than those of a normal population.

negative: Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19 Background: The coronavirus disease 2019 (COVID-19) has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy. Methods: We selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults. Results: Pharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDI) of DCTs were predicted, while 112 of them have been reported. Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, -interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate. Conclusions: At least 17 drugs for COVID-19 therapy with predictable pharmacogenes should be carefully utilized in risk races which are consisted of more risk allele carriers. At least 29 drugs with potential of DDIs are reported to be affected by other DDIs, they should be replaced by similar drugs without interaction if it is possible. Drugs which specifically targeted to infected cells with ACE2 such as chloroquine are preferred in COVID-19 therapy.

negative: COVID-19: Dados Atualizados e sua Relação Com o Sistema Cardiovascular./ COVID-19: Dados Atualizados e sua Relação Com o Sistema Cardiovascular./ COVID-19: Updated Data and its Relation to the Cardiovascular System In December 2019, a new human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) by the World Health Organization, emerged in the city of Wuhan, China. Spreading globally, it is now considered pandemic, with approximately 3 million cases worldwide at the end of April. Its symptoms include fever, cough, and headache, but the main one is shortness of breath. In turn, it is believed that there is a relationship between COVID-19 and damage to the heart muscle, and hypertensive and diabetic patients, for example, seem to have worse prognosis. Therefore, COVID-19 may worsen in individuals with underlying adverse conditions, and a not negligible number of patients hospitalized with this virus had cardiovascular or cerebrovascular diseases. Systemic inflammatory response and immune system disorders during disease progression may be behind this association. In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell. There is, however, no scientific evidence to support the interruption of these drugs. Since they are fundamental for certain chronic diseases, the risk and benefit of their withdrawal in this scenario should be carefully weighed. Finally, cardiologists and health professionals should be aware of the risks of infection and protect themselves as much as possible, sleeping properly and avoiding long working hours.

negative: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

negative: COPD exacerbations: defining their cause and prevention Summary Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.

negative: Predicting Discharge to Institutional Long-Term Care After Stroke: A Systematic Review and Metaanalysis. BACKGROUND/OBJECTIVES Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. DESIGN We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. SETTING Acute and rehabilitation hospitals. PARTICIPANTS Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. MEASUREMENTS Factors associated with new institutionalization. RESULTS From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. CONCLUSION Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting.

negative: Society of gynecologic oncology surgery considerations during when to operate, hesitate and reintegrate the COVID-19 pandemic The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the American College of Surgeons, U.S. Surgeon General, and other surgical professional specialties have recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges are particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to pause, and re-integrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, surgical training, and preparations for the post-COVID-19 peak and surgical re-integration are reviewed.

negative: COVID-19 Pandemic: A Neurological Perspective Even though severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed to principally affect the respiratory system, neurological involvements have already been reported in some published work. We have reviewed original articles, case reports, and existing open-source data-sets to delineate the spectrum of neurological disorders potentially observed in SARS-CoV-2 positive cases. Neurological involvement in coronavirus disease 2019 (COVID-19) corresponds to three situations: (a) neurological manifestations of viral infection, (b) post-infective neurological complications, and (c) infection in patients with neurological co-morbidity. Neurological manifestations can further be subdivided into the central nervous system (headache, dizziness, alteration of the sensorium, ataxia encephalitis, stroke, and seizures) and peripheral nervous system (skeletal muscle injury and peripheral nerve involvement including hyposmia and hypogeusia) symptomatology. Post-infective neurological complications include demyelinating conditions. Reduced mobility and dementia as co-morbidities may predispose a patient to have a viral infection. It is concluded that the pandemic of COVID-19 presents for a neurologist some unique challenges. We observe that SARS-CoV-2 may have various neurological manifestations and in many cases, neurological features may precede typical respiratory symptoms.

negative: Diagnosis of human coronavirus infection by immunofluorescence: Method and application to respiratory disease in hospitalized children Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.

negative: Potential Treatments for COVID-19; a Narrative Literature Review SARS-CoV-2 is a newly emerging human infectious coronavirus that causes COVID-19, which has been recognized as a pandemic by the World Health Organization (WHO) on March 11(th). There is still no vaccine or definitive treatment for this virus because its pathogenesis and proliferation pathways are still unknown. Therefore, in this article, new potential COVID-19 therapies are briefly reviewed.

negative: School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.

negative: Corona Virus (COVID-19) “Infodemic” and Emerging Issues through a Data Lens: The Case of China Coronavirus (COVID-19) is a humanitarian emergency, which started in Wuhan in China in early December 2019, brought into the notice of the authorities in late December, early January 2020, and, after investigation, was declared as an emergency in the third week of January 2020. The WHO declared this as Public Health Emergency of International Concern (PHEIC) on 31th of January 2020, and finally a pandemic on 11th March 2020. As of March 24th, 2020, the virus has caused a casualty of over 16,600 people worldwide with more than 380,000 people confirmed as infected by it, of which more than 10,000 cases are serious. Mainly based on Chinese newspapers, social media and other digital platform data, this paper analyzes the timeline of the key actions taken by the government and people over three months in five different phases. It found that although there was an initial delay in responding, a unique combination of strong governance, strict regulation, strong community vigilance and citizen participation, and wise use of big data and digital technologies, were some of the key factors in China’s efforts to combat this virus. Being inviable and non-measurable (unlike radioactive exposure), appropriate and timely information is very important to form the basic foundation of mitigation and curative measures. Infodemic, as it is termed by WHO, is a key word, where different stakeholder’s participation, along with stricter regulation, is required to reduce the impact of fake news in this information age and social media. Although different countries will need different approaches, focusing on its humanitarian nature and addressing infodemic issues are the two critical factors for future global mitigation efforts.

negative: Neurological manifestations associated with COVID-19: a review and a call for action While the epidemic of Coronavirus disease 2019 (COVID-19) continues to spread globally, more and more evidences are collected about the presence of neurological manifestations and symptoms associated with it. A systematic review has been performed of papers published until 5 April 2020. 29 papers related to neurological manifestations associated with COVID-19 were examined. The results show presence of central and peripheral nervous system manifestations related to coronavirus. Neurological manifestations, or NeuroCOVID, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of CNS symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. Further clinical, epidemiological, and basic science research is urgently needed to understand and address neurological sequalae of COVID-19. Concomitant risk factors or determinants (e.g. demographic factors, comorbidities, or available biomarkers) that may predispose a person with COVID-19 to neurological manifestations also need to be identified. The review shows that although more and more papers are reporting neurological manifestations associated with COVID-19; however, many items remain unclear and this uncertainty calls for a global action that requires close coordination and open-data sharing between hospitals, academic institutions and the fast establishment of harmonised research priorities and research consortia to face the NeuroCOVID-19 complications.

negative: Kidney Allograft Recipients Diagnosed with Coronavirus Disease-2019: A Single Center Report Background: Organ graft recipients receiving immunosuppressive therapy are likely to be at heighted risk for the Coronavirus Disease 2019 (Covid-19) and adverse outcomes including death. It is therefore important to characterize the clinical course and outcome of Covid-19 in this vulnerable population and identify therapeutic strategies that are safe. Methods: We performed a retrospective chart review of 54 adult kidney transplant patients diagnosed with Covid-19 and managed in New York State, the epicenter of Covid-19 pandemic. The patients were evaluated by video visits, phone interviews, or in the Emergency Room for respiratory illness symptoms consistent with Covid-19 from March 13, 2020 to April 20, 2020. Characteristics of the patients were stratified by hospitalization status and disease severity. Clinical course including alterations in immunosuppressive therapy were retrieved from their electronic medical records. Primary outcomes included recovery from Covid-19 symptoms, acute kidney injury, graft failure, and case fatality rate. Results: Of the 54 SARS-Cov-2 positive kidney transplant recipients, 39 with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. Hospitalized patients compared to non-hospitalized patients were more likely to be male, of Hispanic ethnicity, and to have cardiovascular disease. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients, and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs. 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients and only one of 15 non-hospitalized patients. Acute kidney injury occurred in 51% of hospitalized patients. Patients with severe disease were more likely to have elevations in inflammatory biomarkers at presentation. At a median of 21 days follow up, 67% of patients have had their symptoms resolved or improved and 33% have persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired. Conclusions: Clinical presentation of Covid-19 in kidney transplant recipients was similar to what has been described in the general population. The case fatality rate in our entire cohort of 54 kidney transplant recipients was reassuringly low and patients with mild symptomology could be successfully managed at home. Data from the pilot study suggest that a strategy of systematic screening and triage to inpatient or outpatient care, close monitoring, and judicious use of immunosuppressive drugs rather than cessation is beneficial.

negative: First case diagnosed with both COVID-19 and dengue virus infections in Bangladesh: Possible dengue prevention strategies amid COVID-19 outbreak

negative: Pandemic Flu: Clinical management of patients with an influenza-like illness during an influenza pandemic

negative: Determining the spatial effects of COVID-19 using the spatial panel data model Abstract This study investigates the propagation power and effects of the coronavirus disease 2019 (COVID-19) in light of published data. We examine the factors affecting COVID-19 together with the spatial effects, and use spatial panel data models to determine the relationship among the variables including their spatial effects. Using spatial panel models, we analyse the relationship between confirmed cases of COVID-19, deaths thereof, and recovered cases due to treatment. We accordingly determine and include the spatial effects in this examination after establishing the appropriate model for COVID-19. The most efficient and consistent model is interpreted with direct and indirect spatial effects.

negative: A data driven analysis and forecast of an SEIARD epidemic model for COVID-19 in Mexico We propose an SEIARD mathematical model to investigate the current outbreak of coronavirus disease (COVID-19) in Mexico. We conduct a detailed analysis of this model and demonstrate its application using publicly reported data. We calculate the basic reproduction number ($R_0$) via the next-generation matrix method, and we estimate the per day infection, death and recovery rates. We calibrate the parameters of the SEIARD model to the reported data by minimizing the sum of squared errors and attempt to forecast the evolution of the outbreak until June 2020. Our results estimate that the peak of the epidemic in Mexico will be around May 2, 2020. Our model incorporates the importance of considering the aysmptomatic infected individuals, because they represent the majority of the infected population (with symptoms or not) and they could play a huge role in spreading the virus without any knowledge.

negative: Information needs and seeking behaviour among health professionals working at public hospital and health centres in Bahir Dar, Ethiopia BACKGROUND: Universal access to information for health professionals is a need to achieve “health for all strategy.” A large proportion of the population including health professionals have limited access to health information in resource limited countries. The aim of this study is to assess information needs among Ethiopian health professionals. METHODS: A cross sectional quantitative study design complemented with qualitative method was conducted among 350 health care workers in Feburary26-June5/2012. Pretested self-administered questionnaire and observation checklist were used to collect data on different variables. Data entry and data analysis were done using Epi-Info version 3.5.1 and by SPSS version19, respectively. Descriptive statistics and multivariate regression analyses were applied to describe study objectives and identify the determinants of information seeking behaviours respectively. Odds ratio with 95% CI was used to assess the association between a factor and an outcome variable. RESULTS: The majority of the respondents acknowledged the need of health information to their routine activities. About 54.0% of respondents lacked access to health information. Only 42.8% of respondents have access to internet sources. Important barriers to access information were geographical, organizational, personal, economic, educational status and time. About 58.0% of the respondents accessed information by referring their hard copies and asking senior staff. Age, sex, income, computer literacy and access, patient size, work experience and working site were significantly associated with information needs and seeking behaviour. CONCLUSIONS: The health information seeking behaviour of health professional was significant. The heaklth facilities had neither informationcenter such as library, nor internet facilities. Conducting training on managing health information, accessing computer and improving infrastructures are important interventions to facilitate evidence based descions.

negative: Management of clozapine treatment during the COVID-19 pandemic Clozapine is the only available treatment for refractory schizophrenia but its use involves frequent physical contact with healthcare workers for the purpose of mandatory blood monitoring. During the COVID-19 pandemic, patients taking clozapine will be self-isolating to reduce the risk of infection, not least because these patients are at high risk of serious illness and fatality because of high rates of diabetes, obesity and pulmonary disease and an increased risk of pneumonia. Problems may also arise because both clozapine-induced myocarditis and neutropenic sepsis share signs and symptoms with COVID-19 (fever, chest pain, dyspnoea, etc.). We recommend decreasing the frequency of physical contacts by extending the blood monitoring interval to 12 weeks in those patients taking clozapine for more than 1 year. To distinguish COVID-19 from clozapine-related physical adverse effects, we suggest an urgent antigen test alongside a full blood count. In those taking clozapine who develop COVID-19, we suggest continuing with clozapine whenever possible (even during ventilation), reducing the dose if necessary in line with blood assay results. Blood monitoring should continue but clozapine should only cease if there is a significant fall in neutrophils (COVID-19 is linked to lymphopenia but not neutropenia). To protect against the likelihood and severity of respiratory infection, we recommend the use of vitamin D in all clozapine patients. Initiation of clozapine is likely to remain problematic while the risk of infection remains, given the degree of physical contact required to assure safety.

negative: Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine

negative: Long-term psychiatric morbidities among SARS survivors Abstract Objective Severe acute respiratory syndrome (SARS) was the first massive infectious disease outbreak of the 21st century. However, it is unlikely that this outbreak will be the last. This study aimed to evaluate the long-term psychiatric morbidities in survivors of SARS. Method This is a cohort study designed to investigate psychiatric complications among SARS survivors treated in the United Christian Hospital 30 months after the SARS outbreak. Psychiatric morbidities were assessed by the Structured Clinical Interview for DSM-IV, the Impact of Events Scale–Revised and the Hospital Anxiety and Depression Scale. Functional outcomes were assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results Ninety subjects were recruited, yielding a response rate of 96.8%. Post-SARS cumulative incidence of DSM-IV psychiatric disorders was 58.9%. Current prevalence for any psychiatric disorder at 30 months post-SARS was 33.3%. One-fourth of the patients had post-traumatic stress disorder (PTSD), and 15.6% had depressive disorders. Conclusion The outbreak of SARS can be regarded as a mental health catastrophe. PTSD was the most prevalent long-term psychiatric condition, followed by depressive disorders. Our results highlight the need to enhance preparedness and competence of health care professionals in detecting and managing the psychological sequelae of future comparable infectious disease outbreaks.

negative: What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in humans in 2012. A systematic literature review was conducted to synthesize current knowledge and identify critical knowledge gaps. Materials and Methods: We conducted a systematic review on MERS-CoV using PRISMA guidelines. We identified 407 relevant, peer-reviewed publications and selected 208 of these based on their contributions to four key areas: virology; clinical characteristics, outcomes, therapeutic and preventive options; epidemiology and transmission; and animal interface and the search for natural hosts of MERS-CoV. Results: Dipeptidyl peptidase 4 (DPP4/CD26) was identified as the human receptor for MERS-CoV, and a variety of molecular and serological assays developed. Dromedary camels remain the only documented zoonotic source of human infection, but MERS-like CoVs have been detected in bat species globally, as well as in dromedary camels throughout the Middle East and Africa. However, despite evidence of camel-to-human MERS-CoV transmission and cases apparently related to camel contact, the source of many primary cases remains unknown. There have been sustained health care-associated human outbreaks in Saudi Arabia and South Korea, the latter originating from one traveler returning from the Middle East. Transmission mechanisms are poorly understood; for health care, this may include environmental contamination. Various potential therapeutics have been identified, but not yet evaluated in human clinical trials. At least one candidate vaccine has progressed to Phase I trials. Conclusions: There has been substantial MERS-CoV research since 2012, but significant knowledge gaps persist, especially in epidemiology and natural history of the infection. There have been few rigorous studies of baseline prevalence, transmission, and spectrum of disease. Terms such as “camel exposure” and the epidemiological relationships of cases should be clearly defined and standardized. We strongly recommend a shared and accessible registry or database. Coronaviruses will likely continue to emerge, arguing for a unified “One Health” approach.

negative: Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA.

negative: Effects of temperature on COVID-19 transmission Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.

negative: Potential inhibitors for 2019-nCoV coronavirus M protease from clinically approved medicines Starting from December 2019, a novel coronavirus, named 2019-nCoV, was found to cause Severe Acute Respiratory (SARI) symptoms and rapid pandemic in China. With the hope to identify candidate drugs for 2019-nCoV, we adopted a computational approach to screen for available commercial medicines which may function as inhibitors for the Mpro of 2019-nCoV. Up to 10 commercial medicines that may form hydrogen bounds to key residues within the binding pocket of 2019-nCoV Mpro were identified, which may have higher mutation tolerance than lopinavir/ritonavir and may also function as inhibitors for other coronaviruses with similar Mpro binding sites and pocket structures.

negative: Discretionary Fiscal Responses to the Covid-19 Pandemic We analyse discretionary fiscal responses to the Covid-19 pandemic. We distinguish policies for three phases of the pandemic: (1) acute overall disruption, (2) initial recovery phase and (3) the longer term. We analyse measures already taken in (1) and consider measures relevant for (2). We distinguish between lump-sum subsidies, such as deferral of tax payments, which may ease financial constraints, and measures which intentionally affect incentives. We also identify factors that are important given the short-term nature of the measures.

negative: Clinical severity of human infection with avian influenza A(H7N9) virus BACKGROUND: Characterizing the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with the avian influenza A(H7N9) virus that has recently emerged in China. METHODS: Among laboratory-confirmed cases of A(H7N9) who were hospitalised, we estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit based on censored data during the currently ongoing outbreak. We also used information on laboratory-confirmed cases detected through sentinel influenza-like illness (ILI) surveillance to estimate the number of symptomatic A(H7N9) virus infections to date and the symptomatic case fatality risk. FINDINGS: Among 123 hospitalised cases, 37 cases had died and 69 had recovered by May 28, 2013. Hospitalised cases had high risks of mortality (36%; 95% confidence interval (CI): 26%–45%), mechanical ventilation or mortality (69%; 95% CI: 60%–77%), and ICU admission or mechanical ventilation or mortality (83%; 95% CI: 76%–90%), and the risk of these severe outcomes increased with age. Depending on assumptions about the coverage of the sentinel ILI network and health-care seeking behavior for cases of ILI associated with A(H7N9) virus infection, we estimated that the symptomatic case fatality risk could be between 160 and 2,800 per 100,000 symptomatic cases. INTERPRETATION: We estimated that the severity of A(H7N9) is somewhat lower than A(H5N1) but higher than seasonal influenza viruses and influenza A(H1N1)pdm09 virus. The estimated risks of fatality among hospitalised cases and symptomatic cases are measures of severity that should not be affected by shifts over time in the probability of laboratory-confirmation of mild cases and should inform risk assessment. FUNDING: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.

negative: Metabolic syndrome and COVID-19: An update on the associated comorbidities and proposed therapies BACKGROUND AND AIMS: Many patients with coronavirus disease 2019 (COVID-19) have comorbidities related to metabolic syndrome (MS) during the disease course. Its presence in different ethnicities and continents places MS as an important risk factor for COVID-19. Adequate understanding of the interplay between MS, COVID-19 and proposed therapies is required for optimum management of these patients. METHODS: We systematically searched the PubMed and Google Scholar databases until June 1st, 2020 and accessed the full text on COVID-19 and MS to prepare a narrative review on this topic. RESULTS: Patients with metabolic disorders like obesity, diabetes, cardiovascular and liver disease may face a higher risk of infection of COVID-19, greatly affecting the development and prognosis of the disease, being associated with significantly worse outcome in these patients. The proposed drugs that are in clinical trial for COVID-19 treatment must be carefully considered for clinical use, especially in patients with MS. CONCLUSION: MS is a risk factor influencing the progression and prognosis of COVID-2019. The drugs currently evaluated for the infection treatment are promising but need further studies to prove their efficacy and safety, due to the adverse effects may be exacerbated by combination therapy or due to viral infection. The development of a vaccine for immunization is still the best long-term solution.

negative: Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.

negative: COVID-19 and Multi-Organ Response Abstract Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multi-organ involvement. Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality. The hyperinflammatory response of the body, coupled with the plausible direct effects of SARS-CoV-2 on body-wide organs via ACE2, has been associated with complications of the disease. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure have precipitated death. Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients. This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multi-organ impact.

negative: Covid-19 in Critically Ill Patients in the Seattle Region — Case Series BACKGROUND: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. METHODS: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. RESULTS: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. CONCLUSIONS: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)

negative: Host response to bovine viral diarrhea virus and interactions with infectious agents in the feedlot and breeding herd Abstract Bovine viral diarrhea viruses (BVDV) have significant impact on beef and dairy production worldwide. The infections are widespread in the cattle populations, and in many production systems, vaccinations are utilized. BVDV strains have the hallmark of adversely affecting the immune system's many components, both the innate and acquired systems. While BVDV do cause primary infections and disease, their role in the pathogenesis of other agents underscores the complexity of viral–bacterial synergy. A greater understanding of the role of the persistently infected (PI) animal resulting from susceptible females infected at a critical stage of pregnancy has permitted acknowledgment of a major source of infection to susceptible animals. Not only do we understand the role of the PI in transmitting infections and complicating other infections, but we now focus attempts to better diagnose and remove the PI animal. Vaccinations now address the need to have an immune population, especially the breeding females in the herd. Biosecurity, detection and removal of the PI, and effective vaccinations are tools for potential successful BVDV control.

negative: Impact of weather indicators on the COVID-19 outbreak: A multi-state study in India The present study examines the impact of weather indicators on the COVID-19 outbreak in the majorly affected states of India. In this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. The Kendall and Spearman rank correlation tests were chosen to conduct the statistical analysis. In this regard, we compiled a daily dataset including confirmed case counts, Recovered case counts, Deceased cases, Average Temperature, Maximum Relative Humidity, Maximum Wind Speed for six most affected states of India during the period of March 25, 2020 to April 24, 2020. We investigated that the average Humidity and Average Temperature seven days ago play a significant role in the recovery of coronavirus cases. The rise in average temperature will improve the recovery rate in the days to come. The cities with very high humidity levels or dry weather conditions have high probabilities of recovery from COVID-19. The findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures.

negative: CoViD-19 and stress in the pandemic: "sanity is not statistical". CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including . The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.

negative: Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data The geographic spread of 2019 novel coronavirus (COVID-19) infections from the epicenter of Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. Using publicly available event-date data from the ongoing epidemic, the present study investigated the incubation period and other time intervals that govern the epidemiological dynamics of COVID-19 infections. Our results show that the incubation period falls within the range of 2-14 days with 95% confidence and has a mean of around 5 days when approximated using the best-fit lognormal distribution. The mean time from illness onset to hospital admission (for treatment and/or isolation) was estimated at 3-4 days without truncation and at 5-9 days when right truncated. Based on the 95th percentile estimate of the incubation period, we recommend that the length of quarantine should be at least 14 days. The median time delay of 13 days from illness onset to death (17 days with right truncation) should be considered when estimating the COVID-19 case fatality risk.

negative: Transcatheter drug delivery through bronchial artery for COVID-19: is it fiction or could it come true? More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise for treatment of COVID-19. Nevertheless, up to date, no drugs have been confirmed as a definitive treatment for COVID-19. Trials such as the SOLIDARITY and RECOVERY are ongoing, and first results were announced in favour of therapy with dexamethasone with a significant trend showing greatest benefit among those patients requiring ventilation. The drawbacks of these trials include exposing the patients to drugs with well-documented systemic adverse effects or unknown complications of novel therapies without proof of clinical benefit. We present here the hypothesis that bronchial artery infusion could be an alternative for systemic drug infusion in COVID-19 trials with superadded benefits of high drug concentration and low systemic adverse effects. The concept of this idea has many uncertainties and no current clinical data to support. Perhaps, the technique should be first applied in animal models to determine its safety and calculate the effective dose of the drugs. Guidelines and reviews of pharmacotherapy for COVID-19 should be implemented for this fiction to come true.

negative: Preparing for the Perpetual Challenges of Pandemics of Coronavirus Infections with Special Focus on SARS-CoV-2 COVID-19, arising from novel, zoonotic coronavirus-2, has gripped the world in a pandemic. The present chapter discusses the current internationally implemented pandemic preparedness strategies succeeding/recommended to curb the COVID-19 threat to humankind. The updated phase-wise categorization of a pandemic as recommended by the WHO is described, and associated innovations in surveillance, response, and medical measures/advisory in practice across the globe are elaborated. From a bird’s eye view, the COVID-19 pandemic management relies on revolutionizing the disease surveillance by incorporating artificial intelligence and data analytics, boosting the response strategies—extensive testing, case isolation, contact tracing, and social distancing—and promoting awareness and access to pharmaceutical and non-pharmaceutical interventions, which are discussed in the present chapter. We also preview the economic bearing of the COVID-19 pandemic.

negative: Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic ABSTRACT Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.

negative: Lessons from mainland China's epidemic experience about the growth rules of infected and recovered cases of COVID-19 worldwide The novel coronavirus disease (COVID-19) that emerged at the end of 2019 has been controlled in mainland China so far, while it is still spreading globally. When the pandemic will end is a question of great concern. A logistic model depicting the growth rules of infected and recovered cases in mainland China may shed some light on this question. We extended this model to 31 countries outside China experiencing serious COVID-2019 outbreaks. The model well explained the data in our study (R2 >0.95). For infected cases, the semi-saturation period (SSP) ranges from 63 to 170 days (March 3 to June 18). The logistic growth rate of infected cases is positively correlated with that of recovered cases, and the same holds for the SSP. According to the linear connection between the growth rules for infected and recovered cases identified from the Chinese data, we predicted that the SSP of the recovered cases outside China ranges from 82 to 196 days (March 22 to July 8). More importantly, we found a strong positive correlation between the SSP of infected cases and the timing of the government's response, providing strong evidence for the effectiveness of rapid epidemic control measures in various countries.

negative: Presepsin in risk stratification of SARS-CoV-2 patients Abstract Background A severe form of pneumonia, is the leading complication of the respiratory Coronavirus disease 2019 (COVID-19), recently renamed SARS-CoV-2. Soluble cluster of differentiation (CD)14 subtype (sCD14-ST also termed presepsin PSP) is a regulatory factor that modulates immune responses by interacting with T and B cells, useful for early diagnosis, prognosis and risk stratification prediction. Methods In 75 consecutive patients suffering from COVID-19 microbiology proven infection, admitted to intensive care unit (ICU, n=21, 28%) and/or in infectious disease ward (IW, n=54, 72%), PSP (Pathfast, Mitsubishi, Japan) has been measured in addition to routine laboratory tests performed during the period of hospitalization (from January to March 2020). Results PSP demonstrates: -statistically significant higher values (Mann-Whitney test) in 6 patients died (median, IQR= 1046, 763-1240; vs 417, 281-678 ng/L, p<0.05); -statistically significant but poor correlations with CRP (r= 0.59 p<0.001), LDH (r=0.52, p<0.001) and PCT (r=0.72, p<0.001) measured at the same day; -a significant relationship between concentrations and ICU stay. In fact patients showing PSP values higher than 250 ng/L (cut-off for risk stratification) did stay in ICU for a significantly longer time (median 17 days, IQR 12-31; p<0.001) than those exhibiting lower values (median 10 days, IQR 7-18). Conclusions The data obtained seems to demonstrate the role of PSP in providing prognostic information in COVID-19 patients, allowing to identify, during the early phase of the monitoring, the patients suffering from a more severe disease which will be hospitalized for a more long time.

negative: Translational Knowledge Map of COVID-19 A translational knowledge map of COVID-19, based on the analysis of scientific papers and networks citation concurrence of terms and keywords of the terms: covid- 19, 2019-ncov and sars-cov-2 in leading databases (MEDLINE, web of Science and Scopus), was constructed. Some fields of the research on covid-19 are connected together, differing in structure, content and evolution.

negative: Framing COVID-19: How we conceptualize and discuss the pandemic on Twitter Doctors and nurses in these weeks are busy in the trenches, fighting against a new invisible enemy: Covid-19. Cities are locked down and civilians are besieged in their own homes, to prevent the spreading of the virus. War-related terminology is commonly used to frame the discourse around epidemics and diseases. Arguably the discourse around the current epidemic will make use of war-related metaphors too,not only in public discourse and the media, but also in the tweets written by non-experts of mass communication. We hereby present an analysis of the discourse around #Covid-19, based on a corpus of 200k tweets posted on Twitter during March and April 2020. Using topic modelling we first analyze the topics around which the discourse can be classified. Then, we show that the WAR framing is used to talk about specific topics, such as the virus treatment, but not others, such as the effects of social distancing on the population. We then measure and compare the popularity of the WAR frame to three alternative figurative frames (MONSTER, STORM and TSUNAMI) and a literal frame used as control (FAMILY). The results show that while the FAMILY literal frame covers a wider portion of the corpus, among the figurative framings WAR is the most frequently used, and thus arguably the most conventional one. However, we conclude, this frame is not apt to elaborate the discourse around many aspects involved in the current situation. Therefore, we conclude, in line with previous suggestions, a plethora of framing options, or a metaphor menu, may facilitate the communication of various aspects involved in the Covid-19-related discourse on the social media, and thus support civilians in the expression of their feelings, opinions and ideas during the current pandemic.

negative: Agent-Level Pandemic Simulation (ALPS) for Analyzing Effects of Lockdown Measures This paper develops an agent-level simulation model, termed ALPS, for simulating the spread of an infectious disease in a confined community. The mechanism of transmission is agent-to-agent contact, using parameters reported for Corona COVID-19 pandemic. The main goal of the ALPS simulation is analyze effects of preventive measures -- imposition and lifting of lockdown norms -- on the rates of infections, fatalities and recoveries. The model assumptions and choices represent a balance between competing demands of being realistic and being efficient for real-time inferences. The model provides quantification of gains in reducing casualties by imposition and maintenance of restrictive measures in place.

negative: Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China Objective: We aimed to investigate clinical features and management of 55 COVID-19 patients in Wuxi, especially severe COVID-19. Methods: Epidemiological, demographic, clinical, laboratory, imaging, treatment, and outcome data of patients were collected. Follow-up lasted until April 6, 2020. Results: All 55 patients included 47 (85.5%) non-severe patients and 8 (14.5%) severe patients. Common comorbidities were hypertension and diabetes. Common symptoms were fever, cough and sputum. Lymphopenia was a common laboratory finding, and ground-glass opacity was a common chest CT feature. All patients received antiviral therapy of α-interferon inhalation and lopinavir-ritonavir tablets. Common complications included acute liver injury and respiratory failure. All patients were discharged. No death was occurred and no medical staff got infected. Patients with severe COVID-19 showed significantly older age, decreased lymphocytes, increased C reactive protein, and higher frequency of bilateral lung infiltration compared to non-severe patients. Significantly more treatments including antibiotic therapy and mechanical ventilation, longer hospitalization stay and higher cost were shown on severe patients. Conclusions: Our study suggested that patients with severe COVID-19 may be more likely to have an older age, present with lymphopenia and bilateral lung infiltration, receive multiple treatments and stay longer in hospital.

negative: Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). Importance Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure Cardiac involvement with COVID-19. Main Outcomes and Measures Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

negative: Core Outcome Set for Clinical Trials of COVID-19 based on Traditional Chinese and Western Medicine Background: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. Methods: A preliminary list of outcomes were developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Frontline clinicians, as well as nurse, methodologist, evidence based-medicine researcher, and staff from the Chinese Clinical Trials Registry participated by video conference to vote. Results: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS include clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (Pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended. Conclusion: A COS for COVID-19 may improve consistency of outcome reporting in clinical trials.

negative: Mechanism of thrombocytopenia in COVID-19 patients Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.

negative: Cardiac Tamponade Secondary to COVID-19 Abstract A 67-year-old female presented with upper respiratory symptoms and was diagnosed with COVID-19. She was found to have a large hemorrhagic pericardial effusion with echocardiographic signs of tamponade and mild left ventricular impairment. Clinical course was complicated by development of Takotsubo cardiomyopathy. She was treated with pericardiocentesis, colchicine, corticosteroids and hydroxychloroquine with improvement in symptoms.

negative: In the name of the greater good? In the event of a pandemic that poses widespread infection and high death rates, the utilitarian mandate to ‘reduce harm’ is the relevant moral value that trumps other ethical considerations. The primacy of a utilitarian approach dictates that those who are in a position to assist the cessation of the most serious outbreaks in whatever role they may have, must be present to provide their services, and those who administer health care must also be present to ensure that all responders are supported and protected to the highest degree.

negative: Expression of transcriptional units using transmissible gastroenteritis coronavirus derived minigenomes and full-length cDNA clones.

negative: Occupational Health Science in the Time of COVID-19: Now more than Ever Workers bear a heavy share of the burden of how countries contend with COVID-19; they face numerous serious threats to their occupational health ranging from those associated with direct exposure to the virus to those reflecting the conflicts between work and family demands. Ten experts were invited to comment on occupational health issues unique to their areas of expertise. The topics include work-family issues, occupational health issues faced by emergency medical personnel, the transition to telework, discrimination against Asian-Americans, work stressors, presenteeism, the need for supportive supervision, safety concerns, economic stressors, and reminders of death at work. Their comments describe the nature of the occupational health concerns created by COVID-19 and discuss both unanswered research questions and recommendations to help organizations reduce the impacts of COVID-19 on workers.

negative: Reining in the CD8+ T cell: Respiratory virus infection and PD-1-mediated T-cell impairment

negative: Coronavirus Disease (COVID-19): A primer for emergency physicians INTRODUCTION: Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. OBJECTIVE: This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. DISCUSSION: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. CONCLUSION: This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.

negative: Viral Discovery and Sequence Recovery Using DNA Microarrays Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.

negative: A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

negative: Successful recovery from severe COVID-19 pneumonia after kidney transplantation: The interplay between immunosuppression and novel therapy including tocilizumab Although immunosuppressed patients may be more prone to SARS-CoV-2 infection with atypical presentation, long-term immunosuppression therapy may provide some sort of protection for severe clinical complications of COVID-19. The interaction between immunosuppression and new antiviral drugs in the treatment of transplanted patients contracting COVID-19 has not yet been fully investigated. Moreover, data regarding the optimal management of these patients are still very limited. We report a case of the successful recovery from severe COVID-19 of a kidney-transplanted patient treated with hydroxychloroquine, lopinavir/ritonavir, steroid, and tocilizumab.

negative: Early prediction of mortality risk among severe COVID-19 patients using machine learning Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally. The number of deaths has increased with the increase in the number of infected patients. We aimed to develop a clinical model to predict the outcome of severe COVID-19 patients early. Methods Epidemiological, clinical, and first laboratory findings after admission of 183 severe COVID-19 patients (115 survivors and 68 nonsurvivors) from the Sino-French New City Branch of Tongji Hospital were used to develop the predictive models. Five machine learning approaches (logistic regression, partial least squares regression, elastic net, random forest, and bagged flexible discriminant analysis) were used to select the features and predict the patients' outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models' performance. Sixty-four severe COVID-19 patients from the Optical Valley Branch of Tongji Hospital were used to externally validate the final predictive model. Results The baseline characteristics and laboratory tests were significantly different between the survivors and nonsurvivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the derivation and external validation sets were 0.895 and 0.881, respectively. The sensitivity and specificity were 0.892 and 0.687 for the derivation set and 0.839 and 0.794 for the validation set, respectively, when using a probability of death of 50% as the cutoff. The individual risk score based on the four selected variables and the corresponding probability of death can serve as indexes to assess the mortality risk of COVID-19 patients. The predictive model is freely available at https://phenomics.fudan.edu.cn/risk_scores/. Conclusions Age, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level of COVID-19 patients at admission are informative for the patients' outcomes.

negative: Potential risks of SARS-Cov-2 infection on reproductive health Abstract The outbreak of 2019 novel coronavirus disease (COVID-19) has been a major epidemic threat all over the world. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focused on its potential risks on reproductive health, including reproductive system and function, as well as gamete and embryo development, which was underpinned by the virus, drugs, chemical disinfectants and panic psychology during the outbreak of COVID-19.

negative: Role of increasing the aerobic capacity on improving the function of immune and respiratory systems in patients with coronavirus (COVID-19): A review Abstract Background and aims COVID-19 is a public world crisis, however, it is a self-limited infection. In COVID-19, the strength of immune and respiratory systems is a critical element. Thus, this review was conducted to demonstrate the short and long term effects of increasing the aerobic capacity on increasing the function and strength of immune and respiratory systems, particularly those essential for overcoming COVID-19 infections and associated disorders. Methods This review was carried out by searching in Web of Science, Scopus, EBSCO, Medline databases. The search was conducted over clinical trials and literature and systematic reviews on the effects of increasing the aerobic capacity on the function and strength of specific immune and respiratory elements essential for overcoming COVID-19 infections. Results This review found that increasing the aerobic capacity could produce short-term safe improvements in the function of immune and respiratory systems, particularly those specific for COVID-19 infections. This could be mainly produced through three mechanisms. Firstly, it could improve immunity by increasing the level and function of immune cells and immunoglobulins, regulating CRP levels, and decreasing anxiety and depression. Secondly, it could improve respiratory system functions by acting as an antibiotic, antioxidant, and antimycotic, restoring normal lung tissue elasticity and strength. Lastly, it could act as a protective barrier to decrease COVID-19 risk factors, which helps to decrease the incidence and progression of COVID-19. Conclusion This review summarizes that increasing the aerobic capacity is recommended because it has potential of improving immune and respiratory functions which would help counter COVID-19.

negative: Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19

negative: COVID-19 pandemic control: balancing detection policy and lockdown intervention under ICU sustainability We consider here an extended SIR model, including several features of the recent COVID-19 outbreak: in particular the infected and recovered individuals can either be detected (+) or undetected (-) and we also integrate an intensive care unit capacity. Our model enables a tractable quantitative analysis of the optimal policy for the control of the epidemic dynamics using both lockdown and detection intervention levers. With parametric specification based on literature on COVID-19, we investigate sensitivity of various quantities on optimal strategies, taking into account the subtle tradeoff between the sanitary and the economic cost of the pandemic, together with the limited capacity level of ICU. We identify the optimal lockdown policy as an intervention structured in 4 successive phases: First a quick and strong lockdown intervention to stop the exponential growth of the contagion; second a short transition phase to reduce the prevalence of the virus; third a long period with full ICU capacity and stable virus prevalence; finally a return to normal social interactions with disappearance of the virus. We also provide optimal intervention measures with increasing ICU capacity, as well as optimization over the effort on detection of infectious and immune individuals.

negative: The key role of palliative care in response to the COVID-19 tsunami of suffering

negative: Cancer, immune suppression and Coronavirus Disease-19 (COVID-19): Need to manage drug safety Abstract The Coronavirus disease (COVID-19) pandemic is disrupting our health environment. As expected, studies highlighted the great susceptibility of cancer patients to COVID-19 and more severe complications, leading oncologists to deeply rethink patient cancer care. This review is dedicated to the optimization of care pathways and therapeutics in cancer patients during the pandemic and aims to discuss successive issues. First we focused on the international guidelines proposing adjustments and alternative options to cancer care in order to limit hospital admission and cytopenic treatment in cancer patients, most of whom are immunocompromised. In addition cancer patients are prone to polypharmacy, enhancing the risk of drug-related problems as adverse events and drug-drug interactions. Due to increased risk in case of COVID-19, we reported a comprehensive review of all the drug-related problems between COVID-19 and antineoplastics. Moreover, in the absence of approved drug against COVID-19, infected patients may be included in clinical trials evaluating new drugs with a lack of knowledge, particularly in cancer patients. Focusing on the several experimental drugs currently being evaluated, we set up an original data board helping oncologists and pharmacists to identify promptly drug-related problems between antineoplastics and experimental drugs. Finally additional and concrete recommendations are provided, supporting oncologists and pharmacists in their efforts to manage cancer patients and to optimize their treatments in this new era related to COVID-19.

negative: Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence BACKGROUND: Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. METHODS: Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. RESULTS: 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. CONCLUSION: The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

negative: Impact of COVID-19 infection on maternal and neonatal outcomes: a review of 287 pregnancies Pregnant women are vulnerable group in viral outbreaks especially in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this review was to identify maternal and neonatal outcomes in available articles on pregnancies affected by COVID-19. The articles that had assessed outcomes of pregnancy and perinatal of women with COVID-19 between Oct 2019 and Apr 30, 2020 without language limitation were considered. All kinds of studies such as case report, case series, retrospective cohort, case control were included. We searched databases, selected relevant studies and extracted data regarding maternal and neonatal outcomes from each article. Data of 287 pregnant women with COVID-19 of 6 countries were assessed from 28 articles between December 8, 2019 and April 6, 2020. Most pregnant women reported in their third trimester, 102 (35.5%) cases were symptomatic at the time of admission. Common onset symptoms, abnormal laboratory findings, and chest computed tomography pattern were fever (51.5%), lymphocytopenia (67.9%), and multiple ground-glass opacities (78.5%) respectively. 93% of all deliveries were done through cesarean section. No maternal mortality and 3 % ICU admission were reported. Vertical transmission was not reported but its possibility was suggested in three neonates. One neonatal death, one stillbirth, and one abortion were reported. All newborns were not breastfed. This review showed fewer adverse maternal and neonatal outcomes in pregnant women with COVID-19 in comparison with previous coronavirus outbreak infection in pregnancy. Limited data are available regarding possibility of virus transmission in utero, during vaginal childbirth and breastfeeding. Effect of COVID-19 on first and second trimester and ongoing pregnancy outcomes in infected mothers is still questionable.

negative: Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study [Background] Since December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce. [Objectives] To investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19. [Methods] Demographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25th December, 2019 to 15th February, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death. [Results] A total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58{+/-}13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was levated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality. [Conclusions] Cardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2 could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.

negative: COVID-19 outbreak in Greece has passed its rising inflection point and stepping into its peak Since the beginning of 2020, COVID-19 is the most urgent and challenging task for the international scientific community, in order to identify its behaviour, track its progress and plan effective mitigation policies. In this study, Greece is the main focus for assessing the national outbreak and estimating the general trends and outlook of it. Multiple data analytics procedures, spectral decomposition and curve-fitting formulations are developed based on the data available at hand. Standard SIEQRDP epidemic modelling is applied for Greece and for the general region around it, providing hints for the outbreak progression in the mid- and long-term, for various infections under-reporting rates. The overall short-term outlook for Greece seems to be towards positive, with a downward trend in infections rate daily increase (i.e., now beyond the exponential growth rate), a possible peak within a few days beyond April 14th, as well as the high availability level of ICU w.r.t. expected demand at peak. On the negative side, the fade-out period seems to be in the order of several months, with high probability of recurrent surges of the outbreak. The mitigation policies for the `next day' should be focused on close tracking of the epidemic via large-scale tests, strict border checking in international travelling and an adaptive plan for selective activation of mitigation measures when deemed necessary.

negative: Novel coronavirus infection and pregnancy

negative: Health resort medicine can be a suitable setting to recover disabilities in patients tested negative for COVID-19 discharged from hospital? A challenge for the future

negative: Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages. Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation. Immunofluorescence imaging of nsp15 mutant virus-infected macrophages revealed significant dispersal of dsRNA early during infection, whereas in WT virus-infected cells, the majority of the dsRNA was associated with replication complexes. The loss of nsp15 activity also resulted in greatly attenuated disease in mice and stimulated a protective immune response. Taken together, our findings demonstrate that coronavirus nsp15 is critical for evasion of host dsRNA sensors in macrophages and reveal that modulating nsp15 stability and activity is a strategy for generating live-attenuated vaccines.

negative: COVID-19 causes unprecedented educational disruption: Is there a road towards a new normal? COVID-19 confronts the education system with a new and massive crisis. What should a “new normal” look like for future generations? How can countries use the innovativeness of the recovery period to “build back better”? This Viewpoint highlights the UNESCO-led Global Coalition for Education initiative, which is seeking solutions to support learners and teachers, as well as governments throughout the recovery process, with a principal focus on inclusion, equity, and gender equality. The Viewpoint also argues that the current crisis is an opportunity for stronger international collaboration, which might provide a better focus and deliver solutions, including digital tools. Resilience and adaptability will be crucial for the next generations to navigate through the present—and any future—pandemic.

negative: Usefulness of Published PCR Primers in Detecting Human Rhinovirus Infection We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)–specific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology.

negative: The sensitivity and specificity analyses of ambient temperature and population size on the transmission rate of the novel coronavirus (COVID-19) in different provinces of Iran Abstract On 10 April 2020, Iran reported 68,192 COVID-19 cumulative cases including 4232 death and 35,465 recovery cases. Numerous factors could influence the transmission rate and survival of coronavirus. On this basis and according to the latest epidemiological researches, both ambient temperature (AT) and population size (PS) can be considered as significant transmissibility factors for coronavirus. The analysis of receiver operating characteristics (ROC) allows measuring the performance of a classification model using the confusion matrix. This study intends to investigate the sensitivity of AT and PS on the transmission rate of the novel coronavirus in different provinces of Iran. For this purpose, the information of each province of Iran including the annual average of AT and the number of healthy and diseased cases are categorized. Subsequently, the sensitivity and specificity analyses of both AT and PS factors are performed. The obtained results confirm that AT and PS have low sensibility and high sensitivity, respectively. Thus, there is no scientific reason to confirm that the number of COVID-19 cases in warmer climates is less than that of moderate or cold climates. Therefore, it is recommended that the cities/provinces with a population of over 1.7 million people have stricter inspections and more precise controls as their management policy.

negative: Prediction of the Development of Pulmonary Fibrosis Using Serial Thin-Section CT and Clinical Features in Patients Discharged after Treatment for COVID-19 Pneumonia OBJECTIVE: To identify predictors of pulmonary fibrosis development by combining follow-up thin-section CT findings and clinical features in patients discharged after treatment for COVID-19. MATERIALS AND METHODS: This retrospective study involved 32 confirmed COVID-19 patients who were divided into two groups according to the evidence of fibrosis on their latest follow-up CT imaging. Clinical data and CT imaging features of all the patients in different stages were collected and analyzed for comparison. RESULTS: The latest follow-up CT imaging showed fibrosis in 14 patients (male, 12; female, 2) and no fibrosis in 18 patients (male, 10; female, 8). Compared with the non-fibrosis group, the fibrosis group was older (median age: 54.0 years vs. 37.0 years, p = 0.008), and the median levels of C-reactive protein (53.4 mg/L vs. 10.0 mg/L, p = 0.002) and interleukin-6 (79.7 pg/L vs. 11.2 pg/L, p = 0.04) were also higher. The fibrosis group had a longer-term of hospitalization (19.5 days vs. 10.0 days, p = 0.001), pulsed steroid therapy (11.0 days vs. 5.0 days, p < 0.001), and antiviral therapy (12.0 days vs. 6.5 days, p = 0.012). More patients on the worst-state CT scan had an irregular interface (59.4% vs. 34.4%, p = 0.045) and a parenchymal band (71.9% vs. 28.1%, p < 0.001). On initial CT imaging, the irregular interface (57.1%) and parenchymal band (50.0%) were more common in the fibrosis group. On the worst-state CT imaging, interstitial thickening (78.6%), air bronchogram (57.1%), irregular interface (85.7%), coarse reticular pattern (28.6%), parenchymal band (92.9%), and pleural effusion (42.9%) were more common in the fibrosis group. CONCLUSION: Fibrosis was more likely to develop in patients with severe clinical conditions, especially in patients with high inflammatory indicators. Interstitial thickening, irregular interface, coarse reticular pattern, and parenchymal band manifested in the process of the disease may be predictors of pulmonary fibrosis. Irregular interface and parenchymal band could predict the formation of pulmonary fibrosis early.

negative: Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazi The current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.

negative: [Pharmacovigilance study on drug-induced cardiac injury during treatment of COVID-19] Because coronavirus disease 2019(COVID-19) is highly contagious and serious, it has posed a major threat to public health worldwide. The curative effects of integrated traditional Chinese medicine and Western medicine in the treatment of COVID-19 have been widely recognized and confirmed. However, medical workers shall pay attention to drug-induced heart injury in clinical application. Based on the guideline from the Diagnosis and Treatment Plans for COVID-19(trial seventh edition), taking the recommended drugs as examples, by Western medicine, traditional Chinese medicine, Chinese herbal injection and integrated traditional Chinese and Western medicine, the study analyzed the basic characteristics of recommended drugs for cardiac injury by means of literature review and bioinformatics methods, and summarized cardiac adverse reactions, toxicity mechanisms, combined pharmacotherapy, special population and drug monitoring, focusing on the clinical manifestations, toxic components, targets and regulatory mechanisms of drug-induced cardiac injury. The findings suggested being vigilant to drug-induced cardiac injury during the treatment of COVID-19, playing the advantages of clinical pharmacists and clinical Chinese pharmacists, improving the knowledge reserve of pharmacovigilance, strengthening the prescription review, medication notification and medication monitoring, promoting rational drug use and paying attention to special populations and high-risk groups. The study aims to provide suggestions and reference for pharmacovigilance and pharmaceutical care for front-line doctors and pharmacists against COVID-19, in order to avoid the occurrence of drug-induced heart injury for patients with COVID-19.

negative: COVID-19, SARS and MERS: are they closely related? Abstract Background The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. Aims To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. Sources The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. Content COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0–2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7–1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. Implications There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

negative: Investigating the cases of novel coronavirus disease (COVID-19) in China using dynamic statistical techniques The initial investigation by local hospital attributed the outbreak of the novel coronavirus disease (COVID-19) to pneumonia with unknown cause that appeared like the 2003 severe acute respiratory syndrome (SARS). The World Health Organization declared COVID-19 as public health emergency after it spread outside China to several countries. Thus, an assessment of the novel coronavirus disease (COVID-19) with novel estimation approaches is essential to the global debate. This study is the first to develop both time series and panel data models to construct conceptual tools that examine the nexus between death from COVID-19 and confirmed cases. We collected daily data on four health indicators namely deaths, confirmed cases, suspected cases, and recovered cases across 31 Provinces/States in China. Due to the complexities of the COVID-19, we investigated the unobserved factors including environmental exposures accounting for the spread of the disease through human-to-human transmission. We used estimation methods capable of controlling for cross-sectional dependence, endogeneity, and unobserved heterogeneity. We predicted the impulse-response between confirmed cases of COVID-19 and COVID-19-attributable deaths. Our study revealed that the effect of confirmed cases on the novel coronavirus attributable deaths is heterogeneous across Provinces/States in China. We found a linear relationship between COVID-19 attributable deaths and confirmed cases whereas a nonlinear relationship was confirmed for the nexus between recovery cases and confirmed cases. The empirical evidence revealed that an increase in confirmed cases by 1% increases coronavirus attributable deaths by ~0.10%–~1.71% (95% CI). Our empirical results confirmed the presence of unobserved heterogeneity and common factors that facilitates the novel coronavirus attributable deaths caused by increased levels of confirmed cases. Yet, the role of such a medium that facilitates the transmission of COVID-19 remains unclear. We highlight safety precaution and preventive measures to circumvent the human-to-human transmission.

negative: CORONAVIRUS IN PREGNANCY AND DELIVERY: RAPID REVIEW AND EXPERT CONSENSUS BACKGROUND Person to person spread of COIVD-19 in the UK has now been confirmed. There are limited case series reporting the impact on women affected by coronaviruses (CoV) during pregnancy. In women affected by SARS and MERS, the case fatality rate appeared higher in women affected in pregnancy compared with non-pregnant women. We conducted a rapid, review to guide management of women affected by COVID -19 during pregnancy and developed interim practice guidance with the RCOG and RCPCH to inform maternity and neonatal service planning METHODS Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies or randomised-controlled trial describing women affected by coronavirus in pregnancy and on neonates. Data was extracted from relevant papers and the review was drafted with representatives of the RCPCH and RCOG who also provided expert consensus on areas where data were lacking RESULTS From 9964 results on PubMed and 600 on MedRxiv, 18 relevant studies (case reports and case series) were identified. There was inconsistent reporting of maternal, perinatal and neonatal outcomes across case reports and series concerning COVID-19, SARS, MERS and other coronaviruses. From reports of 19 women to date affected by COVID-19 in pregnancy, delivering 20 babies, 3 (16%) were asymptomatic, 1 (5%) was admitted to ICU and no maternal deaths have been reported. Deliveries were 17 by caesarean section, 2 by vaginal delivery, 8 (42%) delivered pre-term. There was one neonatal death, in 15 babies who were tested there was no evidence of vertical transmission. CONCLUSIONS Morbidity and mortality from COVID-19 appears less marked than for SARS and MERS, acknowledging the limited number of cases reported to date. Pre-term delivery affected 42% of women hospitalised with COVID-19, which may put considerable pressure on neonatal services if the UK reasonable worse-case scenario of 80% of the population affected is realised. There has been no evidence of vertical transmission to date. The RCOG and RCPCH have provided interim guidance to help maternity and neonatal services plan their response to COVID-19.

negative: Measuring Human and Economic Activity from Satellite Imagery to Support City-Scale Decision-Making during COVID-19 Pandemic The COVID-19 outbreak forced governments worldwide to impose lockdowns and quarantines over their population to prevent virus transmission. As a consequence, there are disruptions in human and economic activities all over the globe. The recovery process is also expected to be rough. Economic activities impact social behaviors, which leave signatures in satellite images that can be automatically detected and classified. Satellite imagery can support the decision-making of analysts and policymakers by providing a different kind of visibility into the unfolding economic changes. Such information can be useful both during the crisis and also as we recover from it. In this work, we use a deep learning approach that combines strategic location sampling and an ensemble of lightweight convolutional neural networks (CNNs) to recognize specific elements in satellite images and compute economic indicators based on it, automatically. This CNN ensemble framework ranked third place in the US Department of Defense xView challenge, the most advanced benchmark for object detection in satellite images. We show the potential of our framework for temporal analysis using the US IARPA Function Map of the World (fMoW) dataset. We also show results on real examples of different sites before and after the COVID-19 outbreak to demonstrate possibilities. Among the future work is the possibility that with a satellite image dataset that samples a region at a weekly (or biweekly) frequency, we can generate more informative temporal signatures that can predict future economic states. Our code is being made available at https://github.com/maups/covid19-satellite-analysis

negative: COVID-19 and Crosstalk With the Hallmarks of Aging Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.

negative: SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Società Italiana di Andrologia e Medicina della Sessualità) PURPOSE: The recent pandemic of severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) has raised several concerns in reproductive medicine. The aim of this review is to summarize available evidence providing an official position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) METHODS: A comprehensive Pubmed, Web of Science, Embase, Medline and Cochrane library search was performed. Due to the limited evidence and the lack of studies, it was not possible to formulate recommendations according to the Oxford 2011 Levels of Evidence criteria. RESULTS: Several molecular characteristics of the SARS-CoV-2 can justify the presence of virus within the testis and possible alterations of spermatogenesis and endocrine function. Orchitis has been reported as a possible complication of SARS-CoV infection, but similar findings have not been reported for SARS-CoV-2. Alternatively, the orchitis could be the result of a vasculitis as COVID-19 has been associated with abnormalities in coagulation and the segmental vascularization of the testis could account for an orchitis-like syndrome. Finally, available data do not support the presence of SARS-CoV-2 in plasma seminal fluid of infected subjects. CONCLUSION: Data derived from other SARS-CoV infections suggest that in patients recovered from COVID-19, especially for those in reproductive age, andrological consultation and evaluation of gonadal function including semen analysis should be suggested. Studies in larger cohorts of currently infected subjects are warranted to confirm (or exclude) the presence of risks for male gametes that are destined either for cryopreservation in liquid nitrogen or for assisted reproduction techniques.

negative: Flavone ingredients can synergistically inhibit NDV infecting cell and improve ND vaccine's protective rate Abstract In order to screen better flavone prescriptions of anti-Newcastle disease virus (NDV), four flavone ingredients of epimedium flavones (EF), baikal skullcap root flavones (BSRF), wild dendranthema flower flavones (WDFF), and sanchi flavones (SF) screened in previous experiments and their prescriptions were added into chicken embryo fibroblast monolayer with three drug-adding modes respectively. The cellular A570 values, the highest virus inhibitory rates and the score based on virus inhibitory rate were calculated to compare their antiviral activity. In immune protective test, the effects of three preparations (EF-BSRF, EF-SF-WDFF-BSRF and EF-WDFF-BSRF screened by the results in vitro experiment) on NDV infection were compared in chickens vaccinated with ND vaccine then challenged with NDV. Blood was regularly sampled for serum antibody titer determination. The pathogenic and dead statuses of chickens were clinically examined. The results indicated that the A570 values of the nine prescriptions, especially the foresaid three prescriptions at almost all concentrations in three drug-adding modes were significantly higher than that of the virus control group. The foresaid three prescriptions presented at the top five of the highest virus inhibitory rate, and located at the highest three of the score rank. The antibody titers and protective rates of the three prescriptions groups were higher than that of VC group, especially EF-SF-WDFF-BSRF group showed significant difference. These results indicated that flavone prescriptions composed with suitable compatibility could possess synergistical action of antiviral effect, ES-SF-WDFF-BSRF prescription could inhibit the cellular infectivity of NDV, improve the protective effect of ND vaccine and would be expected to exploit into a new-type antiviral drug.

negative: The impact of postoperative complications on the recovery of elderly surgical patients. BACKGROUND While the negative impact of postoperative complications on hospital costs, survival, and cancer recurrence is well known, few studies have quantified the impact of postoperative complications on patient-centered outcomes such as functional status. The objective of this study was to estimate the impact of postoperative complications on recovery of functional status after elective abdominal surgery in elderly patients. METHODS Elderly patients (70 years and older) undergoing elective abdominal surgery, with a planned length of stay >1 day, were prospectively enrolled between July 2012 and December 2014. The primary outcome was time to recovery to the preoperative functional status measured by the short physical performance battery (SPPB) preoperatively and at 1 week, 1, 3, and 6 months after surgery. The comprehensive complication index was calculated to grade the severity and number of postoperative complications. A Weibull survival model with interval censoring was performed, controlling for age, sex, body mass index (BMI), comorbidities (Charlson comorbidity index-CCI), frailty, presence of cancer, nutritional status, wound class, preoperative functional status, and surgical approach. RESULTS Hundred and forty-nine patients (79 men and 70 women) were included in the analysis. Mean age was 77.7 ± 4.9 years, mean BMI was 27.2 ± 5.5 kg/m(2), and the median CCI was 3 (IQR 2-6). The mean preoperative SPPB score was 9.62 ± 2.33. A total of 52 patients (34.9 %) experienced one or more postoperative complications, including four mortalities, and a total of 72 complications. The mean comprehensive complication index score for these patients was 25.7 ± 23.8. In the presence of all other variables included in the model, a higher comprehensive complication index score was found to significantly decrease the hazard of recovery (HR 0.96, CI 0.94-0.98, p value = 0.0004) and hence increase the time to recovery. CONCLUSION Following elective abdominal surgery, elderly patients who experience a greater number and more severe postoperative complications take longer to return to their preoperative functional status.

negative: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 × 10(4) to 1.7 × 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.

negative: Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of ∼5 days (range, 2–14 days). Average age of hospitalized patients has been 49–56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54–73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17–29% of hospitalized patients. Overall case fatality rate appears to be ∼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

negative: [Maternal and neonatal consequences of coronavirus COVID-19 infection during pregnancy: a scoping review]. BACKGROUND Coronavirus disease 2019 (COVID-19) is a new pathology, declared a public health emergency by the World Health Organization, which can have negative consequences for pregnant women and their newborns. The aim of this study was to explore the available knowledge on the consequences of developing COVI-19 in pregnant women and their neonates. METHODS Scoping Review, in which the search for articles was conducted using DeCS ("pregnancy", "coronavirus", "health") and MeSH ("pregnan*", "pregnant women", "coronavirus"), linking the terms with the Boolean AND operator. Databases used were Web of Science, Scopus, BVS, Scielo and CUIDEN. In addition, the PRISMA methodology was applied. RESULTS Ten studies were identified that assessed maternal and neonatal health after maternal COVID-19 infection. Pregnant women seem to had no serious symptoms. Neonates appeared to be affected to a greater extent. A death was reported in a premature newborn whose mother had COVID-19 pneumonia. There did not appear to be vertical transmission from mother to child. Nevertheless, this information was not conclusive. CONCLUSIONS COVID-19 appears to be more benign with pregnant women than with their neonates.

negative: Anosmia and ageusia are emerging as symptoms in patients with COVID-19: What does the current evidence say? There have been several reports noting anosmia and ageusia as possible symptoms of COVID-19. This is of particular interest in oncology since patients receiving some cancer treatments such as chemotherapy or immune therapy often experience similar symptoms as side-effects. The purpose of this report was to summarise the evidence on the existence of anosmia and ageusia an emerging COVID-19 symptoms in order to better inform both oncology patients and clinicians. Currently, there is no published evidence or case reports noting anosmia or ageusia as symptoms of COVID-19. Nevertheless, experts in rhinology have suggested that the onset of such symptoms could either act as a trigger for testing for the disease where possible, or could be a new criterion to self-isolate. Whilst more data is currently needed to strengthen our knowledge of the symptoms of COVID-19, oncology patients who are concerned about anosmia or ageusia in the context of their systemic anti-cancer therapy should contact their acute oncology support line for advice.

negative: Predicting Covid-19's spread in Africa: rural and relatively young population may limit the spread and severity Introduction: A novel coronavirus disease 2019 (COVID-19) has spread to all regions of the world. There is great uncertainty regarding how countries characteristics will affect the spread of the epidemic; to date, there are few studies that attempt to predict the spread of the epidemic in African countries. In this paper, we investigate the role of demographic patterns, urbanization and co-morbidities on the possible trajectories of COVID-19 in Ghana, Kenya, and Senegal. Methods: We use an augmented deterministic SIR model to predict the true spread of the disease, under the containment measures taken so far. We dis-aggregate the infected compartment into asymptomatic, mildly symptomatic, and severely symptomatic to match observed clinical development of COVID-19. We also account for age structures, urbanization, and co-morbidities (HIV, tuberculosis, anemia). Results: In our baseline model, we project that the peak of active cases will occur in July, subject to the effectiveness of policy measures. When accounting for the urbanization, and factoring-in co-morbidities, the peak may occur between June 2nd and June 17th (Ghana), July 22 and August 29 (Kenya), and finally May 28th and June15th. Successful containment policies could lead to even lower rates of severe infections. While most cases will be mild, we project accounting for rural areas and comorbidities and in the absence of policies further containing the spread that between 0.78 and 1.03%, 0.61 and 1.22%, and 0.60 and 0.84% of individuals in Ghana, Kenya, and Senegal will be actively infected and develop severe symptoms at the peak of the epidemic. Conclusion: Compared to Europe, Africa's younger and rural population may modify the severity of the epidemic. The large youth population may lead to more infections but most of these infections will be asymptomatic or mild, and will probably go undetected. The higher prevalence of underlying conditions must be considered.

negative: A Study of Knowledge Sharing related to Covid-19 Pandemic in Stack Overflow The Covid-19 outbreak, beyond its tragic effects, has changed to an unprecedented extent almost every aspect of human activity throughout the world. At the same time, the pandemic has stimulated enormous amount of research by scientists across various disciplines, seeking to study the phenomenon itself, its epidemiological characteristics and ways to confront its consequences. Information Technology, and particularly Data Science, drive innovation in all related to Covid-19 biomedical fields. Acknowledging that software developers routinely resort to open question and answer communities like Stack Overflow to seek advice on solving technical issues, we have performed an empirical study to investigate the extent, evolution and characteristics of Covid-19 related posts. In particular, through the study of 464 Stack Overflow questions posted mainly in February and March 2020 and leveraging the power of text mining, we attempt to shed light into the interest of developers in Covid-19 related topics and the most popular technological problems for which the users seek information. The findings reveal that indeed this global crisis sparked off an intense and increasing activity in Stack Overflow with most post topics reflecting a strong interest on the analysis of Covid-19 data, primarily using Python technologies.

negative: Treatment guidance for lung cancer patients during the COVID-19 pandemic Abstract The global COVID-19 pandemic continues to escalate at a rapid pace inundating medical facilities and creating significant challenges globally. The risk of SARS-CoV-2 infection in cancer patients appears to be higher especially as they are more likely to present with an immunocompromised condition, either from the cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection remain poorly characterized currently and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause significant disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary co-morbidities are more likely to have increased risk and mortality from COVID-19 as one of its common manifestation is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.

negative: The multifaceted long-term effects of the COVID-19 pandemic on urology The COVID-19 pandemic has resulted in immediate effects on urological practice, in particular the vast reduction in elective surgeries. These changes are likely to have long-term effects for both patients and for urologists, which will persist even after the pandemic resolves. The many facets of COVID-19’s effects on urology remain to be seen, but they might also offer opportunities to reassess and improve patient management in urology and beyond.

negative: A Review of Coronavirus Disease-2019 (COVID-19) There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.

negative: Psychological impact of anti-Asian stigma due to the COVID-19 pandemic: A call for research, practice, and policy responses The COVID-19 pandemic is linked to a rise in stigma and discrimination against Chinese and other Asians, which is likely to have a negative impact on mental health, especially when combined with additional outbreak-related stressors. We discuss the need to consider the potential harms of these anti-Asian sentiments during both the height of the pandemic and longer-term recovery through (a) research-examining how it affects mental health and recovery; (b) practice-implementing evidence-based stigma reduction initiatives; and (c) policy-coordinating federal response to anti-Asian racism including investment in mental health services and community-based efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Untersuchung zur Wirkung von Kinesio-Tape und IQ-Tape auf die neuromuskuläre Aktivität beim Joggen, Treppensteigen und Drop-Jump./ [Examination of the Effects of Kinesiotape and IQ Tape on Neuromuscular Activity during Running, Stair Climbing and Drop Jumps]

negative: Cancer care in the time of COVID-19—a perspective from Pakistan Across much of the world, cancer care has been sidelined to a variable degree by the global effort against the coronavirus pandemic. This paper discusses the impact of coronavirus infection on cancer diagnosis and treatment in two leading cancer centres in Pakistan. It also describes the effect that preparations for the expected surge in cases in Pakistan over the next few weeks have had on cancer care. There is an urgent need to evaluate the effect of delays in diagnosis and treatment on cancer stage and treatment, and to decide how to minimise these during likely future cycles of lockdown over the coming months and years.

negative: Tracking the evolution of the SARS coronavirus using high-throughput, high-density resequencing arrays. Mutations in the SARS-Coronavirus (SARS-CoV) can alter its clinical presentation, and the study of its mutation patterns in human populations can facilitate contact tracing. Here, we describe the development and validation of an oligonucleotide resequencing array for interrogating the entire 30-kb SARS-CoV genome in a rapid, cost-effective fashion. Using this platform, we sequenced SARS-CoV genomes from Vero cell culture isolates of 12 patients and directly from four patient tissues. The sequence obtained from the array is highly reproducible, accurate (>99.99% accuracy) and capable of identifying known and novel variants of SARS-CoV. Notably, we applied this technology to a field specimen of probable SARS and rapidly deduced its infectious source. We demonstrate that array-based resequencing-by-hybridization is a fast, reliable, and economical alternative to capillary sequencing for obtaining SARS-CoV genomic sequence on a population scale, making this an ideal platform for the global monitoring of SARS-CoV and other small-genome pathogens.

negative: Cardiothoracic robotic assisted surgery in times of COVID-19 The coronavirus disease 2019 (COVID-19) pandemic poses an immense threat to healthcare systems worldwide. At a time when elective surgeries are being suspended and questions are being raised about how the remaining procedures on COVID-19 positive patients can be performed safely, it is important to consider the potential role of robotic assisted surgery within the current pandemic. Recently, several robotic assisted surgery societies have issued their recommendations. To date, however, no specific recommendations are available for cardiothoracic robotic assisted surgery in COVID-19 positive patients. Here, we discuss the potential risks, benefits, and preventive measures that need to be taken into account when considering robotic assisted surgery for cardiothoracic indications in patients with confirmed COVID-19. It is suggested that robotic assisted surgery might have various advantages such as early recovery after surgery, shorter hospital stay, and reduced loss of blood and fluids as well as smaller incisions. However, electrosurgical and ultrasonic devices, as well as CO2 insufflation should be managed with caution to prevent the risk of aerosolization of viral particles.