query: what causes death from Covid-19?

positive: 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.

positive: Full spectrum of COVID-19 severity still being depicted

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/m2; 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, HbA1c, 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.

positive: Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7–13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

positive: A Machine Learning Model Reveals Older Age and Delayed Hospitalization as Predictors of Mortality in Patients with COVID-19 Objective: The recent pandemic of novel coronavirus disease 2019 (COVID-19) is increasingly causing severe acute respiratory syndrome (SARS) and significant mortality. We aim here to identify the risk factors associated with mortality of coronavirus infected persons using a supervised machine learning approach. Research Design and Methods: Clinical data of 1085 cases of COVID-19 from 13th January to 28th February, 2020 was obtained from Kaggle, an online community of Data scientists. 430 cases were selected for the final analysis. Random Forest classification algorithm was implemented on the dataset to identify the important predictors and their effects on mortality. Results: The Area under the ROC curve obtained during model validation on the test dataset was 0.97. Age was the most important variable in predicting mortality followed by the time gap between symptom onset and hospitalization. Conclusions: Patients aged beyond 62 years are at higher risk of fatality whereas hospitalization within 2 days of the onset of symptoms could reduce mortality in COVID-19 patients.

positive: 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.

positive: Acute kidney injury in SARS-CoV-2 infected patients

positive: Acute Myocardial Injury at Hospital Admission is Associated with All-cause Mortality in COVID-19

positive: The modified NUTRIC score can be used for nutritional risk assessment as well as prognosis prediction in critically ill COVID-19 patients Summary Background and Aims In the newly emerged Coronavirus Disease 2019 (COVID-19) disaster, little is known about the nutritional risks for critically ill patients. It is also unknown whether the modified Nutrition Risk in the Critically ill (mNUTRIC) score is applicable for nutritional risk assessment in intensive care unit (ICU) COVID-19 patients. We set out to investigate the applicability of the mNUTRIC score for assessing nutritional risks and predicting outcomes for these critically ill COVID-19 patients. Methods This retrospective observational study was conducted in three ICUs which had been specially established and equipped for COVID-19 in Wuhan, China. The study population was critically ill COVID-19 patients who had been admitted to these ICUs between January 28 and February 21, 2020. Exclusion criteria were as follows: 1) patients of <18 years; 2) patients who were pregnant; 3) length of ICU stay of <24 hours; 4) insufficient medical information available. Patients’ characteristics and clinical information were obtained from electronic medical and nursing records. The nutritional risk for each patient was assessed at their ICU admission using the mNUTRIC score. A score of ≥5 indicated high nutritional risk. Mortality was calculated according to patients’ outcomes following 28 days of hospitalization in ICU. Results A total of 136 critically ill COVID-19 patients with a median age of 69 years (IQR: 57-77), 86 (63%) males and 50 (37%) females, were included in the study. Based on the mNUTRIC score at ICU admission, a high nutritional risk (≥5 points) was observed in 61% of the critically ill COVID-19 patients, while a low nutritional risk (<5 points) was observed in 39%. The mortality of ICU 28-day was significantly higher in the high nutritional risk group than in the low nutritional risk group (87% vs 49%, P <0.001). Patients in the high nutritional risk group exhibited significantly higher incidences of acute respiratory distress syndrome, acute myocardial injury, secondary infection, shock and use of vasopressors. Additionally, use of a multivariate Cox analysis showed that patients with high nutritional risk had a higher probability of death at ICU 28-day than those with low nutritional risk (adjusted HR =2.01, 95% CI: 1.22-3.32, P =0.006). Conclusions A large proportion of critically ill COVID-19 patients had a high nutritional risk, as revealed by their mNUTRIC score. Patients with high nutritional risk at ICU admission exhibited significantly higher mortality of ICU 28-day, as well as twice the probability of death at ICU 28-day than those with low nutritional risk. Therefore, the mNUTRIC score may be an appropriate tool for nutritional risk assessment and prognosis prediction for critically ill COVID-19 patients.

positive: Hemoglobin value may be decreased in patients with severe coronavirus disease 2019

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: Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome The mortality of Coronavirus disease 2019 (COVID-19) appears to be driven by acute respiratory distress syndrome (ARDS) and a dysregulated immune response to SARS-CoV-2. Emerging evidence suggests that a subset of COVID-19 is characterized by the development of a cytokine storm syndrome (CSS), and interleukin (IL)-6 levels are predictors of COVID-19 severity and in-hospital mortality. Targeting hyper-inflammation in COVID-19 may be critical for reducing mortality. Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (α1-AR) signaling. Prophylactic inhibition of catecholamine synthesis with the α1-AR antagonist prazosin reduced catecholamines and cytokine responses in mice, and resulted in markedly increased survival following various hyper-inflammatory stimuli. These findings offer a rationale for studying α1-AR antagonists in the prophylaxis of patients with COVID-19-CSS and ARDS. As high infection rates threaten to overwhelm hospital capacity during this pandemic, preventative approaches that ameliorate COVID-19 severity and reduce excessive mortality are desperately needed. We hypothesize that treatment with prazosin of individuals who test positive for SARS-CoV-2 could reduce catecholamine surges, secondary cytokine dysregulation, and mortality. To investigate a potential role for α1-AR antagonists in preventing poor outcomes in ARDS, we conducted a retrospective analysis of hospitalized patients diagnosed with ARDS. Using data from the Truven Health MarketScan Research Database (2010-2017), we identified 13,125 men (age 45-64) with ARDS, of whom 655 patients (5.0%) were prescribed α1-AR antagonists in the previous year. Applying logistic regression models, we found that patients with prior use of α1-AR antagonists had lower odds of invasive mechanical ventilation compared to non-users (adjusted OR=0.75, 95% CI 0.59-0.95, p=0.019). Perhaps more importantly, those patients had a ~36% lower incidence of both being ventilated and dying in the hospital (adjusted OR=0.59, 95% CI 0.34-0.95, p=0.042). By contrast, prior use of beta-adrenergic receptor (β-AR) antagonists was not correlated with either outcome. We extended these analyses to patients admitted with pneumonia. Of 108,956 subjects in this cohort, 5,498 patients (5.0%) were taking α1-AR antagonist. Similar to ARDS, patients with pneumonia on α1-AR antagonists (but no β-AR antagonists) had a lower odds of mechanical ventilation (adjusted OR=0.83, 95% CI 0.75-0.92, p<0.001) and of both being ventilated and dying in the hospital (adjusted OR=0.77, 95% CI 0.62-0.94, p=0.014) compared to non-users. Mirroring findings from pre-clinical models, these data support a clinical rationale to study α1-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19. Prospective, randomized clinical trials of alpha-1 receptor antagonists (e.g. prazosin) administered prior to the onset of severe symptoms are needed to assess their efficacy in preventing CSS and reducing mortality in COVID-19.

positive: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. METHODS: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. FINDINGS: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. INTERPRETATION: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

positive: 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.

positive: Caution on Kidney Dysfunctions of COVID-19 Patients Summary Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21th,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding: None.

positive: 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.

positive: The clinical course and its correlated immune status in COVID-19 pneumonia Abstract Objectives To explore the clinical course and its dynamic features of immune status in COVID-19 patients and find predictors correlated with severity and prognosis of COVID-19. Methods The electronic medical records of 204 patients with COVID-19 pneumonia confirmed by nucleic acid testing were retrospectively collected and analyzed. Results All Patients were divided into severe (69) and non-severe group (135). Lymphocyte subsets count, including CD3 + T cell, CD4 + T cell, CD8 + T cell, B cell (CD19+) and NK cell (CD16 + 56+), were significantly lower in severe group (P＜0.001). The dynamic levels of T lymphocytes in severe group were significantly lower from disease onset, but in the improved subgroup the value of T lymphocyte began to increase after about 15-day treatment and finally returned to the normal level. The cut-off value of the counts of CD3+ (576), CD4+ (391) and CD8+ (214) T cell were calculated and indicated significantly high sensitivity and specificity for severity of COVID-19. Conclusion Our results shown that the decrease of CD3+, CD4+ and CD8 + T lymphocyte correlated with the course of patients with COVID-19 pneumonia, especially in severe cases. The level of T lymphocyte could be used as an indicator for prediction of severity and prognosis of patients with COVID-19 pneumonia. The application of glucocorticoid should be cautious in severe cases.

positive: Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections Background SARS-CoV-2 is the cause of an ongoing pandemic with a projected 100,000 to 240,000 U.S. deaths. To date, documentation of histopathologic features in fatal cases of COVID-19 has been limited due to small sample size and incomplete organ sampling. Methods Post-mortem examinations were performed on 12 fatal COVID-19 cases in Washington State during February-March 2020. Clinical and laboratory data were reviewed. Tissue examination of all major organs was performed by light microscopy and electron microscopy. The presence of viral RNA in sampled tissues was tested by RT-PCR. Results All 12 patients were older with significant preexisting comorbidities. The major pulmonary finding was diffuse alveolar damage in the acute and/or organizing phases with virus identified in type I and II pneumocytes by electron microscopy. The kidney demonstrated viral particles in the tubular epithelium, endothelium, and podocytes without significant inflammation. Viral particles were also observed in the trachea and large intestines. SARS-CoV-2 RNA was detected in the cardiac tissue of a patient with lymphocytic myocarditis. RT-PCR also detected viral RNA in the subcarinal lymph nodes, liver, spleen, and large intestines. Conclusion SARS-CoV-2 represents the third novel coronavirus to cause widespread human disease since 2002. Similar to SARS and MERS, the primary pathology was diffuse alveolar damage with virus located in the pneumocytes. However, other major organs including the heart and kidneys may be susceptible to viral replication and damage leading to increased mortality in those with disseminated disease. Understanding the pathology of SARS-CoV-2 will be essential to design effective therapies.

positive: The kidney in COVID-19: protagonist or figurant? The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as "at high risk" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.

positive: Covid-19: Death rate in England and Wales reaches record high because of covid-19

positive: 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.

positive: Multivariate Analysis of Black Race and Environmental Temperature on COVID-19 In the US BACKGROUND: There has been much interest in environmental temperature and race as modulators of Coronavirus disease-19 (COVID-19) infection and mortality. However, in the United States race and temperature correlate with various other social determinants of health, comorbidities, and environmental influences that could be responsible for noted effects. This study investigates the independent effects of race and environmental temperature on COVID-19 incidence and mortality in United States counties. METHODS: Data on COVID-19 and risk factors in all United States counties was collected. 661 counties with at least 50 COVID-19 cases and 217 with at least 10 deaths were included in analyses. Upper and lower quartiles for cases/100,000 people and halves for deaths/100,000 people were compared with t-tests. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of race and environmental temperature. RESULTS: Multivariate regression analyses demonstrated Black race is a risk factor for increased COVID-19 cases (OR=1.22, 95% CI: 1.09-1.40, P=0.001) and deaths independent of comorbidities, poverty, access to health care, and other risk factors. Higher environmental temperature independently reduced caseload (OR=0.81, 95% CI: 0.71-0.91, P=0.0009), but not deaths. CONCLUSIONS: Higher environmental temperatures correlated with reduced COVID-19 cases, but this benefit does not yet appear in mortality models. Black race was an independent risk factor for increased COVID-19 cases and deaths. Thus, many proposed mechanisms through which Black race might increase risk for COVID-19, such as socioeconomic and healthcare-related predispositions, are inadequate in explaining the full magnitude of this health disparity.

positive: Coronavirus (COVID-19) in Haiti: A Call for Action Recently, the cholera outbreak in Haiti demonstrated just how unprepared the country is to rapidly isolate an outbreak of this magnitude, and its vulnerability to the COVID-19 pandemic. This communication briefly examines the health system in Haiti and its vulnerability toward the COVID-19 outbreak.

positive: Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China This case series describes the characteristics of a cohort of patients who died of coronavirus disease 2019 in China.

positive: 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.

positive: Is diet partly responsible for differences in COVID-19 death rates between and within countries? Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

positive: 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.

positive: Epidemiological trends of COVID-19 epidemic in Italy over March 2020: From 1000 to 100 000 cases The coronavirus disease 2019 epidemic started in Italy by the end of January 2020 and, after 1 month, it affected 1049 persons. Based on the Italian Ministry of Health data, we reconstructed the daily course of virus-positive cases and deaths over March 2020 for the whole of Italy, 19 regions and 2 provinces. From 29 February to 31 March, there was a 100.9-fold increase in the cumulative number of cases and a 428.6-fold increase in the number of deaths in Italy. When plotted on a semilogarithmic scale, the curves tended to diverge from linearity with 23%, 16%, and 7% average daily increases during the three decades of March. Similarly, the number of deaths decreased from an average daily growth of 19% over the second decade to 10% over the third decade. The correlation coefficients relating the days to cases or deaths over each one of the three decades approached unity. As inferred from the equations of the regression lines relative to the three decades, the doubling times of cases were 3.4, 5.1, and 9.6 days, respectively. The doubling times of deaths over the second and third decades were 4.9 and 7.0 days, respectively. There was a broad geographic variability, with a striking gradient from the North, where 40.8% of cases and 57.9% of deaths occurred in Lombardy, to the South. On the whole, over March there was a trend to epidemic growth decline but the time for the end of the epidemic will depend on a variety of factors and, at present, it is unpredictable.

positive: Systematic Review and Meta-Analysis of Sex-Specific COVID-19 Clinical Outcomes To successfully mitigate the extraordinary devastation caused by the Coronavirus disease 2019 (COVID-19) pandemic, it is crucial to identify important risk factors for this disease. One such neglected health determinant is the sex of the patient. This is an essential clinical characteristic, as it can factor into a patient's clinical management and preventative measures. Some clinical studies have shown disparities in the proportion between males and females that have more severe clinical outcomes or, subsequently, die from this disease. However, this association has not been unequivocally established. Thus, the purpose of this investigation was to examine the association between male sex and COVID-19 severity. We systematically reviewed the literature, identified non-randomized studies that matched predetermined selection criteria, and performed a meta-analysis to evaluate the proportion of males among four disease severity categories. Appropriate assessment strategies were implemented to assess and minimize potential biases. The results of this meta-analysis indicated that males constituted a significantly higher proportion of those who had adverse clinical outcomes and died from COVID-19. As the coronavirus spread from the East to the West, male sex remained a consistent risk factor. Our results support the establishment of the male sex as an important risk factor for this disease. Early identification and appropriate medical care for males with lab-confirmed COVID-19 may substantially change the course of clinical prognosis, resulting in greater numbers of lives saved.

positive: Association of the insulin resistance marker TyG index with the severity and mortality of COVID-19 BACKGROUND: The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. This study aims to evaluate the association of the TyG index with the severity and mortality of coronavirus disease 2019 (COVID-19). METHODS: The study included a cohort of 151 patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan. Regression models were used to investigate the association between TyG with severity and mortality of COVID-19. RESULTS: In this cohort, 39 (25.8%) patients had diabetes, 62 (41.1%) patients were severe cases, while 33 (22.0%) patients died in hospital. The TyG index levels were significantly higher in the severe cases and death group (mild vs. severe 8.7 ± 0.6 vs. 9.2 ± 0.6, P < 0.001; survivor vs. deceased 8.8 ± 0.6 vs. 9.3 ± 0.7, P < 0.001), respectively. The TyG index was significantly associated with an increased risk of severe case and mortality, after controlling for potential confounders (OR for severe case, 2.9, 95% CI 1.2–6.3, P = 0.007; OR for mortality, 2.9, 95% CI 1.2–6.7, P = 0.016). The associations were not statistically significant for further adjustment of inflammatory factors. CONCLUSION: TyG index was closely associated with the severity and morbidity in COVID-19 patients, thus it may be a valuable marker for identifying poor outcome of COVID-19.

positive: COVID-19: time for paradigm shift in the nexus between local, national and global health

positive: Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

positive: 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.

positive: Risk factors for death in 1859 subjects with COVID-19 We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.04; 95% Confidence Interval [CI], 1.03, 1.06 per year increase; P < 0.001); (2) smoking (HR = 1.84 [1.17, 2.92]; P = 0.009); (3) admission temperature per °C increase (HR = 1.32 [1.07, 1.64]; P = 0.009); (4) Log(10) neutrophil-to-lymphocyte ratio (NLR; HR = 3.30 [2.10, 5.19]; P < 0.001); (5) platelets per 10 E + 9/L decrease (HR = 0.996 [0.994, 0.998]; P = 0.001); (6) activated partial thromboplastin (aPTT) per second increase (HR = 1.04 [1.02, 1.05]; P < 0.001); (7) Log(10) D-dimer per mg/l increase (HR = 3.00 [2.17, 4.16]; P < 0.001); and (8) Log(10) serum creatinine per μmol/L increase (HR = 4.55 [2.72, 7.62]; P < 0.001). In piecewise linear regression analyses Log(10)NLR the interval from ≥0.4 to ≤1.0 was significantly associated with an increased risk of death. Our data identify covariates associated with risk of in hospital death in persons with COVID-19.

positive: Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data

positive: Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate forCOVID-19: Meta-analysis and sensitivity analysis The coronavirus disease 2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscripts conduct a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% interval (2.41, 3.90), the average incubation time to be 5.08 days with the 95% confidence interval (4.77, 5.39) (in day), the asymptomatic infection rate to be 46% with the 95% confidence interval (18.48%, 73.60%), and the case fatality rate to be 2.72% with 95% confidence interval (1.29%, 4.16%) where asymptomatic infections are accounted for.

positive: Epidemiological and clinical features of 200 hospitalized patients with Corona Virus Disease 2019 outside Wuhan, China: A descriptive study BACKGROUND: The recent outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide, with especially severe epidemics occurring in cities across China. OBJECTIVES: To report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. STUDY DESIGN: 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8, 2020 were investigated retrospectively. The epidemiological data and clinical characteristics were collected. The data between the ICU patients and non-ICU patients were compared. The patients were followed up till Feb 26, 2020. RESULTS: Of the 200 hospitalized patients with COVID-19, 98 (49.0%) were male, and the mean age was 55 years. Eighty-seven (43.5%) had no linkage to Wuhan or contact history. Familial clustering was found in 34 patients. Sixtyfive (32.5%) suffered from chronic diseases. The common symptoms included fever (171[85.5%]), cough (116[58.0%]), and fatigue (64[32%]). Most patients had lymphopenia. One hundred and seventy-two (86%) patients showed typical imaging findings of viral pneumonia. Most patients received antiviral, antibiotic, and corticosteroid treatment. Compared with the non-ICU patients, 29 (14.5%) patients in the ICU were older and more likely to show dyspnea and complications including ARDS. As of Feb 26, 15 (51.7%) patients in the ICU had died. CONCLUSIONS: The COVID-19 infection was of clustering onset and can cause severe respiratory disease and even death. The mortality of ICU patients with COVID-19 was considerably high.

positive: Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19) The epicenter of the original outbreak in China has high male smoking rates of around 50%, and early reported death rates have an emphasis on older males, therefore the likelihood of smokers being overrepresented in fatalities is high. In Iran, China, Italy, and South Korea, female smoking rates are much lower than males. Fewer females have contracted the virus. If this analysis is correct, then Indonesia would be expected to begin experiencing high rates of Covid-19 because its male smoking rate is over 60% (Tobacco Atlas). Smokers are vulnerable to respiratory viruses. Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. This could also be true for new electronic smoking devices such as electronic cigarettes and “heat-not-burn” IQOS devices. ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation. Data on smoking status should be collected on all identified cases of Covid-19.

positive: Risk factors for mortality in pregnant women with SARS-CoV-2 infection Since the first case of pneumonia was described, SARS-CoV-2 infection (coronavirus disease [COVID]-19) rapidly spread worldwide With 94,288 infections and more than 10,000 deaths, Mexico is the third Latin-American country in number of confirmed cases and second in mortality1. A major risk factor for adverse outcome in COVID-19 infection is the presence of advance age, co-morbidities including diabetes, hypertension and obesity among other non-communicable diseases2. Epidemiological data from high-prevalence countries reveal that compared to men, women are less likely to die or to require hospital admission to intensive care. This may suggest that pregnant women are not more susceptible to infection or to experience serious complications. However, whether the presence of co-morbidities or advanced maternal age confers a higher risk of adverse outcome in pregnant women with COVID-19 is unknown3. In this research letter, we aimed at evaluating the risk factor associated with maternal mortality secondary to COVID-19 infection in a middle-income country. Advanced maternal age is linked to an increased risk of mortality, while diabetes is the most important risk factor for maternal death. This is partly explained by an increasing incidence of non-communicable diseases in women of advanced age which is a common feature in most countries4. In the last decades, low- and middle-income countries have experienced accelerated socio-cultural changes associated with its incorporation into the international economic community, which have increased the number of obese and diabetic population, including pregnant women5. This has caused an increased risk for complications and fatality among COVID-19 positive population2,3. Thus, policies for reducing obesity and diabetes in low- and middle-income countries are most needed to reduce the mortality of COVID-19 in pregnant women.

positive: Mortality of COVID-19 is Associated with Cellular Immune Function Compared to Immune Function in Chinese Han Population In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in Chinese Han population is limited. Our objective is to describe the clinical characteristics of SARS-CoV-2 pneumonia compared to normal controls in the Chinese Han population. In this case series of 752 patients, the full spectrum of cases is described. Fever was present in 86-90% of the patients. The second most common symptom was cough (49.1-51.0%), fatigue (25.2-27.1%), sputum (20.0-23.1%), and headache (9.8-11.1%). the mortality rate is 4.6% in Wuhan, 1.9% in Beijing, and 0.9% in Shanghai. Our findings showed that the levels of lymphocytes were 0.8（IQR, 0.6-1.1）109/L in Wuhan, 1.0（IQR, 0.7-1.4）109/L in Beijing, and 1.1 (IQR, 0.8-1.5) 109/L in Shanghai before admission to hospitals, respectively, indicating that cellular immune function might relate to the mortality. Based on the reference ranges of normal Chinese Han population and the data of the critically ill patients we have observed, it is recommended that reference ranges of people at high risk of COVID-19 infection are CD3+ lymphocytes below 900 cells/mm3, CD4+ lymphocytes below 500 cells/mm3, and CD8+ lymphocytes below 300 cells/mm3.

positive: Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system.

positive: The Disproportionate Impact of COVID-19 on Minority Groups: A Social Justice Concern

positive: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study OBJECTIVE: Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS: This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS: Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and they were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

positive: Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

positive: Letter to the Editor: Variability but not admission or trends in NEWS2 score predicts clinical outcome in elderly hospitalised patients with COVID-19 • In elderly COVID-19 inpatients, admission NEWS2 scores did not predict mortality. • Of components of NEW2 score, only systolic blood pressure predicted mortality. • A high variability in NEW2 score predicted mortality. • NEWS2 score does not consider the degree of supplemental oxygen patients require. • A more sensitive early warning score for COVID-19 is needed.

positive: Genomic, geographic and temporal distributions of SARS-CoV-2 mutations The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.

positive: Abnormal liver function tests predict transfer to intensive care unit and death in COVID‐19 BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID‐19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non‐critically ill patients with COVID‐19. METHODS: In this multicenter, retrospective study, we collected data about 565 inpatients with COVID‐19. Data on LFTs were collected at admission and every 7±2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20vs8%; p<0.001), acute kidney injury (22vs13%, p=0.009), need for mechanical ventilation (14vs6%; p=0.005), and mortality (21vs11%; p=0.004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR=3.53; p<0.001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID‐19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.

positive: Thromboinflammation and the hypercoagulability of COVID-19

positive: 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.

positive: Trends in excess cancer and cardiovascular deaths in Scotland during the COVID-19 pandemic 30 December 2019 to 20 April 2020 Understanding the trends in causes of death for different diseases during the current COVID-19 pandemic is important to determine whether there are excess deaths beyond what is normally expected. Using the most recent report from National Records Scotland (NRS) on 29 April 2020, we examined the percentage difference in crude numbers of deaths in 2020 compared to the average for 2015-2019 by week of death within calendar year. To determine if trends were similar, suggesting underreporting/underdiagnosed COVID-19 related deaths, we also looked at the trends in % differences for cardiovascular disease deaths. From the first 17 weeks' of data, we found a peak in excess deaths between weeks 14 of 2020, about four weeks after the first case in Scotland was detected on 1 March 2020-- but by week 17 these excesses had diminished around the time lockdown in the UK began. Similar observations were seen for cardiovascular disease-related deaths. These observations suggest that the short-term increase in excess cancer and cardiovascular deaths might be associated with undetected/unconfirmed deaths related to COVID-19. Both of these conditions make patients more susceptible to infection and lack of widespread access to testing for COVID-19 are likely to have resulted in under-estimation of COVID-19 mortality. These data further suggest that the cumulative toll of COVID-19 on mortality is likely undercounted. More detailed analysis is needed to determine if these excesses were directly or indirectly related to COVID-19. Disease specific mortality will need constant monitoring for the foreseeable future as changes occur in increasing capacity and access to testing, reporting criteria, changes to health services and different measures are implemented to control the spread of the COVID-19. Multidisciplinary, multi-institutional, national and international collaborations for complementary and population specific data analysis is required to respond and mitigate adverse effects of the COVID-19 pandemic and to inform planning for future pandemics.

positive: Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. METHODS: This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. RESULTS: In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41-68; range, 20-91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were >65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n=52), dry cough (69.1%; n=38), and chest distress (63.6%; n=35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. CONCLUSIONS: In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multi-organ involvement and death, as compared with younger patients.

positive: COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus. The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

positive: Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer’s dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.

positive: COVID -19 outbreak – Diabetes aspect and perspective

positive: Covid-19: Death rate in England and Wales reaches record high because of covid-19.

positive: [Comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease 2019] Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) shared similar pathogenetic, clinical and pathological features. Fever and cough were the most common symptoms of both diseases, while myalgia and diarrhea were less common in patients with COVID-19. Acute respiratory distress syndrome (ARDS) was the most severe pulmonary complication that caused high mortality rate. Histologically, diffuse alveolar damage (DAD) was the most characteristic finding in non-survivors with either SARS or COVID-19. Cases of patients died less than 10-14 days of disease duration demonstrated acute-phase DAD, while cases beyond 10-14 days of disease duration exhibited organizing-phase DAD in SARS. Meanwhile, organization and fibrosis were usually accompanied by exudation. Coronavirus was mostly detected in pneumocytes, but less in macrophages and bronchiolar epithelial cells. Hemorrhagic necrosis and lymphocyte depletion were found in lymph nodes and spleen in both SARS and COVID-19, indicating a pathological basis of lymphocytopenia. Thrombosis was commonly observed in small vessels and microvasculaturr in lungs accompanying DAD. Microthrombosis was also found in extrapulmonary organs in COVID-19, that was less reported in SARS. Damages in multiple extrapulmonary organs were observed, but coronavirus was not detected in some of those organs, indicating an alternative mechanism beyond viral infection, such as hypoxemia, ischemia and cytokine storm induced immunological injury. DAD due to viral infection and immunological injury, as well as multi-organ dysfunction and extensive microthrombus formation, brought huge challenge to the management of patients with severe SARS or COVID-19.

positive: Acute kidney injury is associated with the mortality of coronavirus disease 2019 We read with great interest the recent article "Analysis of 92 deceased patients with COVID-19" by Yang et al. published in the Journal of medical virology. The authors observed that 14 patients suffered renal injury after infection of SARS-CoV-2 in 92 deceased patients with coronavirus disease 2019 (COVID-19), although none of them had chronic renal insufficiency. This article is protected by copyright. All rights reserved.

positive: Changes in epithelial secretory cells and potentiation of neurogenic inflammation in the trachea of rats with respiratory tract infections In rats respiratory tract infections due to Sendai virus and coronavirus usually are transient, but they can have long-lasting consequences when accompanied by Mycoplasma pulmonis infections. Morphological alterations in the tracheal epithelium and a potentiation of the inflammatory response evoked by sensory nerve stimulation (“neurogenic inflammation”) are evident nine weeks after the infections begin, but the extent to which these changes are present at earlier times is not known. In the present study we characterized these abnormalities in the epithelium and determined the extent to which they are present 3 and 6 weeks after the infections begin. We also determined the magnitude of the potentiation of neurogenic inflammation at these times, whether the potentiation can be reversed by glucocorticoids, and whether a proliferation of blood vessels contributes to the abnormally large amount of plasma extravasation associated with this potentiation. To this end, we studied Long-Evans rats that acquired these viral and mycoplasmal infections from other rats. We found that the tracheal epithelium of the infected rats had ten times as many Alcian blue-PAS positive mucous cells as did that of pathogen-free rats; but it contained none of the serous cells typical of pathogen-free rats, so the total number of secretory cells was not increased. In addition, the epithelium of the infected rats had three times the number of ciliated cells and had only a third of the number of globule leukocytes. In response to an injection of capsaicin (150 μg/kg i.v.), the tracheas of the infected rats developed an abnormally large amount of extravasation of two tracers Evans blue dye and Monastral blue pigment, and had an abnormally large number of Monastral blue-labeled venules, particularly in regions of mucosa overlying the cartilaginous rings. This abnormally large amount of extravasation was blocked by dexamethasone (1 mg/day i.p. for 5 days). We conclude that M. pulmonis infections, exacerbated at the outset by viral infections, result within three weeks in the transformation of epithelial serous cells into mucous cells, the proliferation of ciliated cells, and the depletion of globule leukocytes. They also cause a proliferation of mediator-sensitive blood vessels in the airway mucosa, which is likely to contribute to the potentiation of neurogenic inflammation that accompanies these infections.

positive: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters OBJECTIVE: To evaluate the relative risk of COVID-19 death in people <65 years old versus older individuals in the general population, to provide estimates of absolute risk of COVID-19 death at the population level, and to understand what proportion of COVID-19 deaths occur in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Countries and US states or major cities with at least 250 COVID-19 deaths as of 4/4/2020 and with information available on death counts according to age strata, allowing to calculate the number of deaths in people with age <65. Data were available for Belgium, Germany, Italy, Netherlands, Portugal, Spain, Sweden, and Switzerland, as well as Louisiana, Michigan, Washington states and New York City as of April 4, 2020. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths that occur in people <65 years old; relative risk of COVID-19 death in people <65 versus ≥65 years old; absolute risk of death in people <65 and in those ≥80 years old in the general population as of 4/4/2020; absolute death risk expressed as equivalent of death risk from driving a motor vehicle. RESULTS: Individuals with age <65 account for 5%-9% of all COVID-19 deaths in the 8 European epicenters, and approach 30% in three US hotbed locations. People <65 years old had 34- to 73-fold lower risk than those ≥65 years old in the European countries and 13- to 15-fold lower risk in New York City, Louisiana and Michigan. The absolute risk of COVID-19 death ranged from 1.7 per million for people <65 years old in Germany to 79 per million in New York City. The absolute risk of COVID-19 death for people ≥80 years old ranged from approximately 1 in 6,000 in Germany to 1 in 420 in Spain. The COVID-19 death risk in people <65 years old during the period of fatalities from the epidemic was equivalent to the death risk from driving between 9 miles per day (Germany) and 415 miles per day (New York City). People <65 years old and not having any underlying predisposing conditions accounted for only 0.3%, 0.7%, and 1.8% of all COVID-19 deaths in Netherlands, Italy, and New York City. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in the hotbeds of the pandemic and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.

positive: Risk factors for disease severity, unimprovement, and mortality of COVID-19 patients in Wuhan, China Abstract Objective Since December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear. Methods All consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020 were enrolled in this retrospective cohort study. Results A total of 663 COVID-19 patients were included in this study. Among those, 247 (37.3%) had at least one kind of chronic disease. A total of 0.5% (n=3) of patients were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical condition, respectively. In our hospital during follow-up, 251 of 663 (37.9%) patients were improved and 25 patients died, leading to a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have severe and critical COVID-19 conditions, show unimprovement, and die (P < 0.001, < 0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95% CI 0.311-0.758; P = 0.001), having severe COVID-19 conditions (OR = 0.129, 95% CI 0.082-0.201; P < 0.001), expectoration (OR = 1.796, 95% CI 1.062-3.036; P = 0.029), muscle ache (OR = 0.309, 95% CI 0.153-0.626; P = 0.001), and decreased albumin (OR = 1.929, 95% CI 1.199-3.104; P = 0.007) were associated with unimprovement in COVID-19 patients. Conclusion Being male, in severe COVID-19 conditions, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.

positive: How many lives can be saved? A global view on the impact of testing, herd immunity and demographics on COVID-19 fatality rates In this work, we assess the global impact of COVID-19 showing how demographic factors, testing policies and herd immunity are key for saving lives. We extend a standard epidemiological SEIR model in order to: (a) identify the role of demographics (population size and population age distribution) on COVID-19 fatality rates; (b) quantify the maximum number of lives that can be saved according to different testing strategies, different levels of herd immunity, and specific population characteristics; and (d) infer from the observed case fatality rates (CFR) what the true fatality rate might be. Different from previous SEIR model extensions, we implement a Bayesian Melding method in our calibration strategy which enables us to account for data limitation on the total number of deaths. We derive a distribution of the set of parameters that best replicate the observed evolution of deaths by using information from both the model and the data.

positive: Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19 Abstract Background Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. Methods A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. Results 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). Conclusions NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.

positive: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 Background Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. Research question The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. Study Design and Methods This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. Results The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the COVID-19 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao 2/Fio 2 of 198.2 mm Hg in the COVID-19 cohort was significantly higher than the Pao 2/Fio 2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). Interpretation There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

positive: Why are more BAME people dying from COVID-19?

positive: 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.

positive: How lethal is the novel coronavirus, and how many undetected cases there are? The importance of being tested. There is big concern for estimating the lethality and the extent of undetected infections associated with the novel coronavirus SARS-CoV2 outbreak. While detailed epidemiological models are certainly needed, I suggest here an orthogonal approach based on a minimum number of parameters robustly fitted from the cumulative data easily accessible for all countries at the John Hopkins University database that became the worldwide reference for the pandemics. I show that, after few days from the beginning of the outbreak, the apparent death rate can be extrapolated to infinite time through regularized regression such as rescaled ridge regression. The variation from country to country of these extrapolated death rates appears to depend almost only (r^2=0.91) on the ratio between performed tests and detected cases even when the instantaneous apparent lethality rates are as different as 9% in Italy and 0.4% in Germany. Extrapolating to the limit of infinite number of tests, I obtain a death rate of 0.012+/- 0.012, in agreement with other estimates. The inverse relationship between the extrapolated death rate and the intensity tests allows estimating that more than 50% of cases were undetected in most countries, with more than 90% undetected cases in countries severely hit by the epidemics such as Italy. Finally, I propose to adopt the ratio between the cumulative number of recovered and deceased persons as an indicator that can anticipate the halting of the epidemics.

positive: Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.

positive: ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19 The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.

positive: Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.

positive: Evidence for ethnic inequalities in mortality related to COVID-19 infections: Findings from an ecological analysis of England and Wales Background In the absence of direct data on ethnic inequalities in COVID-19 related mortality in the UK, we examine the relationship between ethnic composition of an area and rate of mortality in the area. Methods Ecological analysis using COVID-19 related mortality rates occurring by 24th April 2020, and ethnic composition of the population, across local authorities in England and Wales. Account is taken of age, population density, area deprivation and pollution. Results For every 1% rise in proportion of the population who are ethnic minority, COVID-19 related deaths increased by 5.10 (3.99 to 6.21) per million. This rise is present for each ethnic minority category examined. The size of this increase is a little reduced in a fully adjusted model, suggesting that some of the association results from ethnic minority people living in more densely populated, more polluted and more deprived areas. This estimate suggests that the average England and Wales COVID-19 related death rate would rise by 25% in a local authority with twice the average number of ethnic minority people. Discussion We find clear evidence that rates of COVID-19 related mortality within a local authority increase as the proportion of the population who are ethnic minority increases. We suggest that this is a consequence of social and economic inequalities, including among key workers, driven by entrenched structural and institutional racism and racial discrimination. We argue that these factors should be central to any investigation of ethnic inequalities in COVID-19 outcomes.

positive: Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: A single center study BACKGROUND: An outbreak of COVID-19 in Iran has spread throughout the country. Identifying the epidemiological characteristics of this disease will help to make appropriate decisions and thus control the epidemic. The aim of this study was characterization of the epidemiological features of COVID-19 in Iran. METHODS: In this retrospective study, data related to the epidemiological characteristics of COVID-19 patients admitted to Baqiyatallah Hospital in Tehran, Iran, from 19 February 2020 to 15 April 2020 have been analyzed and reported. Patient characteristics including age, gender and underlying diseases were investigated. Data were collected through patient records. Sex ratio, Case Fatality Rate (CFR) and daily trend of cases were also determined. A multiple logistic regression analysis was also performed to assess affecting factors on mortality. RESULTS: From February 19, 2020 to April 15, 2020, 12870 patients referred to the hospital emergency department, of which 2968 were hospitalized with COVID-19 diagnosis. The majority of cases were in the age group of 50 to 60 years of old. The male-to-female ratio was 1.93:1. A total of 239 deaths occurred among all cases for an overall CFR of 1.85% based on the total number of patients (both outpatient and inpatient) and 8.06% among hospitalized patients. Out of all patients 10.89% had comorbidity. Diabetes, chronic respiratory diseases, hypertension, cardiovascular diseases, chronic Kidney diseases and cancer were the most common comorbidities with 3.81, 2.02 , 1.99 , 1.25, 0.60 and 0.57 %, respectively. Male gender (OR=1.45, 95% CI: 1.08-1.96), older age (OR=1.05, 95% CI: 1.04-1.06) and having underlying diseases (OR=1.53, 95% CI: 1.04-2.24) were significantly associated with mortality. CONCLUSIONS: The results of this study showed that Male gender, older age and having comorbidities were significantly associated with the risk of death among COVID-19 patients. It is important to pay special attention to male elderly patients with underlying diseases.

positive: Sudden cardiac death in COVID-19 patients, a report of three cases The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1–6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.

positive: 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.

positive: Current data on the cardiovascular effects of the COVID-19

positive: How Could This Happen?: Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS) In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.

positive: Effects of pre-existing morbidities on occurrence of death among COVID-19 disease patients: A systematic review and meta-analysis Abstract Background: Coronavirus disease 2019 (COVID-19), most hectic pandemic of the era, is increasing exponentially and taking thousands of lives, worldwide. Objective: This study aimed to assess the prevalence of pre-existing morbidities among COVID-19 infected patients and their mortality risks against each type of pre-existing morbidity categories. Design: Systematic review and meta-analysis Data sources: Medline, Web of Science, Scopus, and CINAHL databases were searched using the following keywords: (COVID-19 or 2019-nCoV or Coronavirus or SARS-CoV-2) AND (Comorbidity or Morbidity) AND (Mortality or Death or Died) up to May 01, 2020. Further searches were conducted using the reference list of the selected studies, renowned pre-print servers (e.g., medRxiv, bioRixv, SSRN), and relevant journal websites. Eligibility criteria: Studies written in the English language included if those were conducted among COVID-19 patients with and without comorbidities and presented survivor vs. non-survivor counts or hazard/odds of deaths or survivors against types of pre-existing morbidities. Methods: Comorbidities reported in the selected studies were grouped into eight categories. The pooled likelihoods of deaths in each category were estimated using a fixed or random-effect model, based on the heterogeneity assessment. Publication bias was assessed by visual inspection of the funnel plot asymmetry and Egger regression test. Trim and Fill method was used if there any publication bias was found. Results: A total of 42 studies included in this study comprised of 39,398 samples. The most common pre-existing morbidities in COVID-19 infected patients were hypertension (36.5%), cardiovascular disease (11.9%), and diabetes (22.0%). The higher likelihood of deaths was found among COVID-19 patients who had pre-existing cardiovascular system diseases (OR: 3.32, 95% CI: 2.79-3.95), immune and metabolic disorders (OR: 2.39, 95% CI: 2.00-2.85), respiratory diseases (OR: 2.02, 95% CI: 1.80-2.26), cerebrovascular system diseases (OR: 4.12, 95% CI: 3.04-5.58), any types of cancers (OR: 2.22, 95% CI: 1.63-3.03), renal (OR: 3.02, 95% CI: 2.60-3.52), and liver system diseases (OR: 1.44, 95% CI: 1.21-1.71). Conclusions: This study provides evidence of a higher likelihood of deaths among COVID-19 patients against morbidity categories. These findings could potentially help healthcare providers to sort out the most endangered COVID-19 patients by comorbidities, take precautionary measures during hospitalization, assess susceptibility to death, and prioritize their treatment, which could potentially reduce the number of fatalities in COVID-19 disease.

positive: Impact of Fundamental Diseases on Patients With COVID-19 OBJECTIVES: In December 2019, a new type of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared in Wuhan, China. Serious outbreaks of coronavirus disease 2019 (COVID-19), related to the SARS-CoV-2 virus, have occurred throughout China and the world. Therefore, we intend to shed light on its potential clinical and epidemiological characteristics. METHODS: In this retrospective study, we included 50 confirmed fatal cases of SARS-CoV-2 reported on Chinese official media networks from January 16, 2020, to February 5, 2020. All the cases were confirmed by local qualified medical and health institutions. Specific information has been released through official channels. According to the contents of the reports, we recorded in detail the gender, age, first symptom date, death date, primary symptoms, chronic fundamental diseases, and other data of the patients, and carried out analyses and discussion. RESULTS: In total, 50 fatal cases were reported: median age was 70 y old, and males were 2.33 times more likely to die than females. The median number of days from the first symptom to death was 13, and that length of time tended to be shorter among people aged 65 and older compared with those younger than 65 (12 days vs 17 days; P = 0.046). Therefore, the older patients had fewer number of days from the first symptom to death (r = -0.40; P = 0.012). CONCLUSIONS: In our study, we found that most of the deaths were elderly men with chronic fundamental diseases, and their COVID-19 progression to death time was shorter. At the same time, we demonstrated that older men are more likely to become infected with COVID-19, and the risk of death is positively correlated with age.

positive: Potential lethal outbreak of coronavirus disease (COVID-19) among the elderly in retirement homes and long-term facilities, France, March 2020 Reports from the coronavirus disease (COVID-19) outbreak in China identified older age as a predictor of severity and mortality [1] A retrospective analysis of individual case data from China and elsewhere showed a very strong age gradient in the infection fatality ratio (IFR) and case fatality ratio (CFR) [2] In France, as at 15 March 2020, people older than 75 years accounted for 20% of the confirmed cases but 79% of the deaths [3] Cardiovascular diseases, hypertension and diabetes mellitus were the comorbidities most frequently associated with COVID-19, and many patients died of their original comorbidities [4,5] All these comorbidities are highly common among dependent elderly people housed in institutions Using simple calculation, we present here the impact of several worst-case scenarios in French institutions Potential number of deathsGo to section We studied different scenarios to simulate the potential death toll of an outbreak of COVID-19 in the French institutions in the absence of mitigation measures We extracted the age structure of residents from 40 “Habitat et Humanisme” institutions for dependent elderly people In France, at the end of 2017, 766,400 people above 60 years of age were housed in retirement homes for dependent elderly people, in long-term care facilities or received home-based care [6] While the calculation of IFR is based on the proportion of all infected cases, i e a precise estimation of the proportion of symptomatic and asymptomatic cases, we restricted our analysis to CFR The CFR, estimated from China and elsewhere, for 60–69 year-olds, 70–79 year-olds and those 80 years and older were, respectively, 3 6%, 8 0% and 14 8% [2] We applied the hypothesis that 30–50% of the institutions were infected, a final attack rate (AR) of 30–50% among the residents and applying age-specific fatality ratios, with their confidence intervals (CI), from [2] By the time the epidemic is over, the resulting death toll in these institutions could be equal to the yearly national death toll caused by seasonal influenza in those older than above 65 years (9,025 deaths on average between 2000 and 2009) or it could largely exceed that figure, depending on the final AR and the proportion of infected institutions (Table) [7] Among this frail population, part of this excess in mortality may be due to the acceleration of underlying unavoidable process and another part directly attributable to the infection

positive: Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning

positive: COVID‐19: diabetes and death. A call to action

positive: Chronic heart diseases as the most prevalent comorbidities among deaths by COVID-19 in Brazil Age, sex and presence of comorbidities are risk factors associated with COVID-19. Hypertension, diabetes and heart disease are the most common comorbidities in patients with COVID-19. The objective of this study was to estimate the prevalence of patients with comorbidities who died of COVID-19 in Brazil. Searches of data were carried out on the official pages of the 26 State health departments and the federal district. The random-effect method was used to calculate the prevalence of patients with comorbidities who died. From the beginning of the pandemic in Brazil until May 20, 2020, 276,703 cases of COVID-19 were notified in Brazil, 6.4% died, 58.6% of whom were male. The prevalence of comorbidities among deaths was 83% (95% CI: 79 - 87), with heart disease and diabetes being the most prevalent. To our knowledge, this study represents the first large analysis of cases of patients with confirmed COVID-19 in Brazil. There is a high prevalence of comorbidities (83%) among patients who died from COVID-19 in Brazil, with heart disease being the most prevalent. This is important considering the possible secondary effects produced by drugs such as hydroxychloroquine.

positive: Two Fatal Cases of Hidden Pneumonia in Young People Abstract: Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by inflammation of the lung parenchyma leading to impaired gas exchange. This condition is often lethal, usually requiring mechanical ventilation and admission to an intensive care unit. We present two fatal cases of hidden pneumonia in young people and discuss the pathophysiological mechanism of ARDS with reference to the histological pattern. A complete forensic approach by means of autopsy and histological, immunohistochemical, and microbiological, examination was carried out. In both cases the cause of death was cardio‐respiratory failure following an acute bilateral pneumonia with diffuse alveolar damage and ARDS associated with sepsis and disseminated intravascular coagulation. Our cases suggest on one side the importance of an early diagnosis to avoid unexpected death while on the other that the diagnosis of ARDS has to be confirmed on the basis of a careful postmortem examination and a complete microscopy and microbiological study.

positive: Testing the association between blood type and COVID-19 infection, intubation, and death The rapid global spread of the novel coronavirus SARS-CoV-2 has strained existing healthcare and testing resources, making the identification and prioritization of individuals most at-risk a critical challenge. A recent study of patients in China discovered an association between ABO blood type and SARS-CoV-2 infection status by comparing COVID-19 patients with the general population. Whether blood type is associated with increased COVID-19 morbidity or mortality remains unknown. We used observational healthcare data on 1559 individuals tested for SARS-CoV-2 (682 COV+) with known blood type in the New York Presbyterian (NYP) hospital system to assess the association between ABO+Rh blood type and SARS-CoV-2 infection status, intubation, and death. We found a higher proportion of blood group A and a lower proportion of blood group O among COV+ patients compared to COV−, though in both cases the result is significant only in Rh positive blood types. We show that the effect of blood type is not explained by risk factors we considered (age, sex, hypertension, diabetes mellitus, overweight status, and chronic cardiovascular and lung disorders). In a meta-analysis of NYP data with previously-reported data from China, we find enrichment for A and B and depletion of O blood groups among COVID-19 patients compared to the general population. Our data do not provide strong evidence of associations between blood group and intubation or death among COVID-19 patients. In this preliminary observational study of data currently being collected during the outbreak, we find new evidence of associations between B, AB, and Rh blood groups and COVID-19 and further evidence of recently-discovered associations between A and O blood groups and COVID-19.

positive: Todesfälle in neun Regionen Italiens im Februar/März 2020: „Mortalitäts-Exzess-Lupe“ für SARS-CoV-2/COVID-19-Epidemiologie in Deutschland Italy is particularly affected by SARS-CoV-2/COVID-19. Recently, Colombo and Impicciatore compared the deaths in 1084 selected municipalities between 21 February 2020 and 21 March 2020 with deaths in the same time period in 2015 to 2019. We extend analyses of data from the Italian National Institute of Statistics (ISTAT) and calculate SMRs for all causes of death in the nine selected regions of Italy, separately for men and women and summarized. We analyze the effect of covariables by Poisson modelling and discuss the limitations of the current elaborations. We conclude: In agreement with Colombo and Impicciatore, in the particular corona situation, this “mortality excess loupe” – assuming otherwise constant determinants of death – can be a virus-test-independent tool to determine mortality effects of SARS-CoV-2. The current “loupe” is focused on municipalities with increases of more than 20% deaths in March 2020 compared to the average deaths on the same days in 2015–2019. The time window of investigation could be opened before 21 February 2020 to detect masked increases in mortality before the first “COVID-19 death” was ascertained. The current “loupe” conveys pronounced mortality increases also in regions that were not considered to be corona hotspots. In this respect, even in the absence of representative virus test results, mortality data can be important indicators of the distribution or spread of a newly acting factor. Overall, it is advisable to carry out SMR analyses for Germany on a regular basis, differentiated by region, gender, age group and cause of death. Such analyses can contribute to the early detection and evaluation of the severity of a deadly pandemic (“burden of disease”) as well as to monitoring the dynamic spread of a factor such as SARS-CoV-2. SMR analyses can also be used to assess and evaluate both desired and undesired effects of measures taken against SARS-CoV-2/COVID-19 – and possibly other epidemics or pandemics.

positive: 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.

positive: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

positive: Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0-72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

positive: Sudden Death from Pulmonary Causes This chapter seeks to survey many of the common pathological entities identified in the lungs at autopsy and the potential role of pulmonary disease in formulating an opinion regarding the cause of death. Appreciation of pulmonary pathology in the medicolegal context is important as it frequently contributes to the immediate or underlying mechanisms of death. The primacy of the lungs in breathing and their coordinated function with the cardiovascular system means that pulmonary failure can rapidly compromise tissue oxygenation and body chemistry, leading to an alteration in blood pH, hypoxic damage to downstream tissues and ultimately multiorgan failure and death. Moreover, given that the lungs have direct contact with the environment through inhalation and receive approximately 50% of the cardiac output with each beat of the heart, they may be adversely affected by hazardous agents from the outside world or other pathologic processes not primarily located in the lungs. The range of topics discussed herein is limited by design to deaths due to disease and largely foregoes discussion of more forensically relevant issues relating to toxicology or trauma. Furthermore, the content and format of this chapter is not intended to be encyclopedic, but rather attempts to highlight selected issues regarding pulmonary disease of potential relevance to surgical or forensic pathologists who perform medicolegal postmortem examinations.

positive: 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.

positive: Todesfälle in neun Regionen Italiens im Februar/März 2020: "Mortalitäts-Exzess-Lupe" für SARS-CoV-2/COVID-19-Epidemiologie in Deutschland./ [Deaths in nine regions of Italy in February/March 2020: "Mortality Excess Loupe" for SARS-CoV-2/COVID-19-Epidemiology in Germany] Italy is particularly affected by SARS-CoV-2/COVID-19. Recently, Colombo and Impicciatore compared the deaths in 1084 selected municipalities between 21 February 2020 and 21 March 2020 with deaths in the same time period in 2015 to 2019. We extend analyses of data from the Italian National Institute of Statistics (ISTAT) and calculate SMRs for all causes of death in the nine selected regions of Italy, separately for men and women and summarized. We analyze the effect of covariables by Poisson modelling and discuss the limitations of the current elaborations. We conclude: In agreement with Colombo and Impicciatore, in the particular corona situation, this "mortality excess loupe" - assuming otherwise constant determinants of death - can be a virus-test-independent tool to determine mortality effects of SARS-CoV-2. The current "loupe" is focused on municipalities with increases of more than 20% deaths in March 2020 compared to the average deaths on the same days in 2015-2019. The time window of investigation could be opened before 21 February 2020 to detect masked increases in mortality before the first "COVID-19 death" was ascertained. The current "loupe" conveys pronounced mortality increases also in regions that were not considered to be corona hotspots. In this respect, even in the absence of representative virus test results, mortality data can be important indicators of the distribution or spread of a newly acting factor. Overall, it is advisable to carry out SMR analyses for Germany on a regular basis, differentiated by region, gender, age group and cause of death. Such analyses can contribute to the early detection and evaluation of the severity of a deadly pandemic ("burden of disease") as well as to monitoring the dynamic spread of a factor such as SARS-CoV-2. SMR analyses can also be used to assess and evaluate both desired and undesired effects of measures taken against SARS-CoV-2/COVID-19 - and possibly other epidemics or pandemics.

positive: The importance of hypertension as a risk factor for severe illness and mortality in COVID‐19 The virus responsible for COVID-19 binds to the angiotensin converting enzyme-2 (ACE-2) receptor [1]. Several articles have noted that hypertension is a risk factor for COVID-19 [2-7]. It is currently difficult to distinguish between hypertension as an independent risk factor in COVID-19 from one that co-varies with other patient factors such as age and cardiovascular disease. It is difficult from individual reports to determine whether hypertension is a risk factor for development of symptomatic disease or hospitalisation or for more severe disease. Reviewing the literature that reports rates of hypertension amongst included patients indicates a consistent association with more severe disease and increased mortality.

positive: Kidney disease is associated with in-hospital death of patients with COVID-19 In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+â¼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+â¼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.

positive: 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,

positive: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.).

positive: Liver Chemistries in COVID-19 Patients with Survival or Death: A Meta-Analysis Background and Aims: Although abnormal liver chemistries are linked to higher risk of death related to coronavirus disease (COVID-19), liver manifestations may be diverse and even confused. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19 patients with death or survival. Methods: We searched PubMed, Google Scholar, medRxiv, bioRxiv, Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19 using a fixed or random-effects model. Results: In the meta-analysis of 18 studies, which included a total of 2,862 patients, the pooled mean alanine aminotransferase (ALT) was 30.9 IU/L in the COVID-19 patients with death and 26.3 IU/L in the COVID-19 patients discharged alive (p < 0.0001). The pooled mean aspartate aminotransferase (AST) level was 45.3 IU/L in the COVID-19 patients with death while 30.1 IU/L in the patients discharged alive (p < 0.0001). Compared with the discharged alive cases, the dead cases tended to have lower albumin levels but longer prothrombin time, and international standardized ratio. Conclusions: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively described three patterns of liver impairment related to COVID-19, hepatocellular injury, cholestasis, and hepatocellular disfunction. Patients died from COVID-19 tend to have different liver chemistries from those are discharged alive. Close monitoring of liver chemistries provides an early warning against COVID-19 related death.

positive: COVID-19 and the role of chronic inflammation in patients with obesity Coronavirus disease 2019 (COVID-19) and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a particular risk to people living with preexisting conditions that impair immune response or amplify pro-inflammatory response. Low-grade chronic systemic inflammation, common in people with obesity, is associated with the development of atherosclerosis, type 2 diabetes, and hypertension, well known comorbidities that adversely affect the outcomes of patients with COVID-19. Risk stratification based on the Edmonton Obesity Staging System (EOSS), which classifies obesity based on the presence of medical, mental, and/or functional complications rather than on body mass index (BMI), has been shown to be a better predictor of all-cause mortality and it may well be that EOSS stages may better describe the risk of hyperinflammation in patients with COVID-19 infection. Analyzing a group of metabolic ill patients with obesity (EOSS 2 and 3), we found an increased interleukin-6 and linear regression analysis showed a positive correlation with C-reactive protein (CRP) (p = 0.014) and waist-to-hip-ratio (WHR) (p = 0.031). Physicians should be aware of these findings in patients with COVID-19 infection. Early identification of possible hyperinflammation could be fundamental and should guide decision making regarding hospitalization, early respiratory support, and therapy with immunosuppression to improve mortality.

positive: Clinical Characteristics and Outcomes of 74 Patients With Severe or Critical COVID-19 BACKGROUND: The outbreak of the coronavirus disease (COVID-19) has led to a major concern and caused a pandemic globally. The goal of this study was to clarify the clinical characteristics of recovery and death in patients with severe or critical COVID-19. MATERIALS AND METHODS: In this retrospective single-center study, clinical data were collected from 74 severe or critical COVID-19 patients in Wuhan Fourth Hospital between Jan. 25th and Feb. 26th, 2020. All patients were divided into a recovery group or a death group according to clinical outcomes, and the differences between the groups were compared. RESULTS: Of the 74 patients enrolled in the study, 48 (64.9%) were severe cases and 26 (35.1%) were critical cases. Sixty (81.1%) patients were recovered and 14 (18.9%) died. Compared with recovery patients, patients in the death group were older, and had higher incidences of hypertension, coronary disease and dyspnea at admission. Laboratory tests for lactate dehydrogenase, creatine kinase, myoglobin, brain natriuretic peptide and D-dimer indicated higher levels in the death group. The PaO2:FiO2 ratio and minimum SpO2 were lower in the death group, and a higher proportion of these patients received noninvasive mechanical ventilation, invasive mechanical ventilation and extracorporeal membrane oxygenation treatment. CONCLUSIONS: Elderly patients with comorbidities are at higher risk of severe COVID-19 or death. Patients with a low blood gas index and poor coagulation function at admission had a high mortality rate. For such patients, comprehensive treatment should be performed as soon as possible to improve the prognosis and reduce mortality.

positive: Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) The world is currently facing a serious SARS-CoV-2 infection pandemic. This virus is a new isolate of coronavirus, and the current infection crisis has surpassed the SARS and MERS epidemics that occurred in 2002 and 2013, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and spreading across more than 130 countries worldwide. The spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, thereby reiterating to the governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of the patients need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of the elderly, especially individuals who are older than 60 years of age, and have comorbidities, including hypertension, diabetes, and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow less susceptible and are not considered as a risk group. Therefore, in this review, we discuss some possible molecular and cellular mechanisms by virtue of which the elderly subjects may be more susceptible to severe COVID-19. Toward this, we raise two main points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe that these points are pivotal for a better understanding of the pathogenesis of severe COVID-19, and must be carefully addressed by physicians and scientists in the field.

positive: Inside the lungs of COVID-19 disease In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.

positive: Elevated D-Dimer Levels are Associated with Increased Risk of Mortality in COVID-19: A Systematic Review and Meta-Analysis Introduction. The 2019 novel Coronavirus (2019 nCoV), now declared a pandemic has an overall case fatality of 2 to 3% but it is as high as 50% in critically ill patients. D-dimer is an important prognostic tool, often elevated in patients with severe COVID-19 infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19 infected patients. Methods. We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality. Results. 18 studies (16 retrospective and 2 prospective) with a total of 3,682 patients met the inclusion criteria. The pooled mean difference (MD) suggested significantly elevated D-dimer levels in patients who died versus those survived (MD 6.13 mg/L, 95% CI 4.16 to 8.11, p <0.001). Similarly, the pooled mean D-dimer levels were significantly elevated in patients with severe COVID-19 infection (MD 0.54 mg/L, 95% CI 0.28 to 0.8, p< 0.001). In addition, the risk of mortality was four-fold higher in patients with positive D-dimer vs negative D-dimer (RR 4.11, 95% CI 2.48 to 6.84, p< 0.001) and the risk of developing the severe disease was two-fold higher in patients with positive D-dimer levels vs negative D-dimer (RR 2.04, 95% CI 1.34 to 3.11, p < 0.001). Conclusion. Our meta-analysis demonstrates that patients with COVID-19 presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.

positive: Acute liver injury and its association with death risk of patients with COVID-19: a hospital-based prospective case-cohort study Background: Coronavirus disease 2019 (COVID-19) is a newly respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze SARS-CoV-2-induced acute liver injury (ALI), its association with death risk and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. ALI was evaluated and its prognosis was tracked. The association between ALI and death risk was analyzed. Results: Of 355 COVID-19 patients, 211 were common, 88 severe, and 51 critical ill cases, respectively. On admission, 223 (62.8%) patients were with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, ALI was more common in critical ill patients. By multivariate logistic regression, male, older age and lymphocyte reduction were three important independent risk factors predicting ALI among COVID-19 patients. Death risk analysis shows that fatality rate was higher among patients with hypoproteinemia than those without hypoproteinemia (RR=9.471, P<0.001). Moreover, fatality rate was higher among patients with cholestasis than those without cholestasis (RR=2.182, P<0.05). Follow-up observation found that more than one hepatic functional indexes of two-third patients remained abnormal 14 days after discharge. Conclusions: ALI at early stage elevates death risk of COVID-19 patients. SARS-CoV-2-induced ALI has not recovered completely 14 days after discharge.

positive: Risk factors influencing the prognosis of elderly patients infected with COVID-19: a clinical retrospective study in Wuhan, China. The mortality rate of elderly patients with Coronavirus Disease 2019 (COVID-19) was significantly higher than the overall mortality rate. However, besides age, leading death risk factors for the high mortality in elderly patients remain unidentified. This retrospective study included 210 elderly COVID-19 patients (aged ≥ 65 years), of whom 175 patients were discharged and 35 died. All deceased patients had at least one comorbidity. A significantly higher proportion of patients in the deceased group had cardiovascular diseases (49% vs. 20%), respiratory diseases (51% vs. 11%), chronic kidney disease (29% vs. 5%) and cerebrovascular disease (20% vs. 3%) than that in the discharged group. The median levels of C-reactive protein (125.8mg/L vs. 9.3mg/L) and blood urea nitrogen (7.2mmol/L vs. 4.4mmol/L) were significantly higher and median lymphocyte counts (0.7×109/L vs. 1.1×109/L) significantly lower in the deceased group than those in the discharged group. The survival curve analysis showed that higher C-reactive protein (≥5mg/L) plus any other abnormalities of lymphocyte, blood urea nitrogen or lactate dehydrogenase significantly predicted poor prognosis of COVID-19 infected elderly patients. This study revealed that the risk factors for the death in these elderly patients included comorbidities, increased levels of C-reactive protein and blood urea nitrogen, and lymphopenia during hospitalization.

positive: Immunodepletion with Hypoxemia: A Potential High Risk Subtype of Coronavirus Disease 2019 Background The outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia, and discuss the relationship between hypoxemia severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient. Methods This is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis. Results Apart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia during the hospitalization, and the severity of hypoxemia was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died. Conclusions We discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis may be a high risk of fatal pneumonia.

positive: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

positive: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.

positive: The differential expression of the ACE2 receptor across ages and gender explains the differential lethality of SARS-Cov-2 and suggests possible therapy The fatality rate of SARS-Cov-2 escalates with age and is larger in men than women. I show that these variations are strongly correlated with the levels of the ACE2 protein in the lungs but surprisingly, despite ACE2 is the viral receptor, higher levels lead to lower fatality. This behaviour is consistent with a previous mathematical model that predicts that the speed of viral progression in the organism has a maximum and then declines with the receptor level. SARS-Cov-2 degrades ACE2 and thus worsens lung injury, causes vasoconstriction, thrombotic problems, and exacerbated inflammatory response. I developed a mathematical model based on the influence of ACE2 on viral propagation and on the negative effects of its degradation. The model fits SARS-CoV-2 fatality rate across age and gender with high accuracy ($r^2>0.9$). Rescaling the model parameters with the binding rates of the spike proteins of SARS-CoV and SARS-CoV-2 allows predicting the fatality rate of SARS-CoV across age and gender, in particular its higher severity for young patients, thus linking the molecular and epidemiological levels. These results support the suggestion that drugs that enhance the expression of ACE2, such as ACE inhibitors and angiotensin receptor blockers, constitute a promising therapy against the most adverse effects of CoViD-19. Furthermore, ACE2 is a candidate prognostic factor for detecting population that needs stronger protection.

positive: SARS-CoV-2: fear versus data ABSTRACT SARS-CoV-2, the novel coronavirus from China, is spreading around the world, causing a huge reaction despite its current low incidence outside China and the Far East. Four common coronaviruses are in current circulation and cause millions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-CoV-2 in Organisation for Economic Co-operation and Development countries. It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing.

positive: Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease BACKGROUND: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD. METHODS: This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities. RESULTS: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14–2.30)) and only DM (1.69 (1.05–2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95% CI 2.09–3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05). CONCLUSIONS: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.

positive: Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China 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: Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

positive: Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency Background: Cancer and multiple non-cancer conditions are considered by the Centers for Disease Control and Prevention (CDC) as high risk conditions in the COVID-19 emergency. Professional societies have recommended changes in cancer service provision to minimize COVID-19 risks to cancer patients and health care workers. However, we do not know the extent to which cancer patients, in whom multi-morbidity is common, may be at higher overall risk of mortality as a net result of multiple factors including COVID-19 infection, changes in health services, and socioeconomic factors. Methods: We report multi-center, weekly cancer diagnostic referrals and chemotherapy treatments until April 2020 in England and Northern Ireland. We analyzed population-based health records from 3,862,012 adults in England to estimate 1-year mortality in 24 cancer sites and 15 non-cancer comorbidity clusters (40 conditions) recognized by CDC as high-risk. We estimated overall (direct and indirect) effects of COVID-19 emergency on mortality under different Relative Impact of the Emergency (RIE) and different Proportions of the population Affected by the Emergency (PAE). We applied the same model to the US, using Surveillance, Epidemiology, and End Results (SEER) program data. Results: Weekly data until April 2020 demonstrate significant falls in admissions for chemotherapy (45-66% reduction) and urgent referrals for early cancer diagnosis (70-89% reduction), compared to pre-emergency levels. Under conservative assumptions of the emergency affecting only people with newly diagnosed cancer (incident cases) at COVID-19 PAE of 40%, and an RIE of 1.5, the model estimated 6,270 excess deaths at 1 year in England and 33,890 excess deaths in the US. In England, the proportion of patients with incident cancer with [≥]1 comorbidity was 65.2%. The number of comorbidities was strongly associated with cancer mortality risk. Across a range of model assumptions, and across incident and prevalent cancer cases, 78% of excess deaths occur in cancer patients with [≥]1 comorbidity. Conclusion: We provide the first estimates of potential excess mortality among people with cancer and multimorbidity due to the COVID-19 emergency and demonstrate dramatic changes in cancer services. To better inform prioritization of cancer care and guide policy change, there is an urgent need for weekly data on cause-specific excess mortality, cancer diagnosis and treatment provision and better intelligence on the use of effective treatments for comorbidities.

positive: Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65â years (OR 3.765, 95% CI 1.146â17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755â8.044; p=0.007), CD3+CD8+ T-cells ≤75â cells·µL-1 (OR 3.982, 95% CI 1.132â14.006; p<0.001) and cardiac troponin I ≥0.05â ng·mL-1 (OR 4.077, 95% CI 1.166â14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75â cells·µL-1 and cardiac troponin I ≥0.05â ng·mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65â years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75â cells·µL-1 and cardiac troponin I ≥0.05â ng·mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

positive: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020. Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.

positive: SARS-CoV-2 (COVID-19) and intravascular volume management strategies in the critically ill The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread across the globe, and millions of people may be affected. While knowledge regarding epidemiologic features and diagnostic tools of coronavirus disease 2019 (COVID-19) is rapidly evolving, uncertainties surrounding various aspects of its optimal management strategies persist. A subset of these patients develop a more severe form of the disease characterized by expanding pulmonary lesions, sepsis, acute respiratory distress syndrome, and respiratory failure. Due to lack of data on treatment strategies specific to this subset of patients, currently available evidence on management of the critically ill needs to be extrapolated and customized to their clinical needs. The article calls attention to fluid stewardship in the critically ill with COVID-19 by judiciously applying the evidence-based resuscitation principles to their specific clinical features such as high rates of cardiac injury. As we await more data from treating these patients, this strategy is likely to help reduce potential complications.

positive: Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 BACKGROUND: Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS: We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS: In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS: In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).

positive: Induced Pluripotent Stem Cells (iPSCs) Derived 3D Human Lung Organoids from Different Ethnicities to Understand the SARS-CoV2 Severity/Infectivity Percentage

positive: Analysis of Characteristics in Death Patients with COVID-19 Pneumonia without Underlying Diseases

positive: Death rate mystery Knowing the true rate of death from covid-19 will help us fight the pandemic, but for the moment it eludes us, reports Michael Le Page

positive: COVID-19: POSTMORTEM DIAGNOSTIC AND BIOSAFETY CONSIDERATIONS As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (e.g. cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with—but not of—COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there are a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for ME/C offices encountering COVID-19 at autopsy.

positive: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.

positive: Considerations for Statin Therapy in Patients with COVID-19

positive: Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.

positive: Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×10(9)/L, CRP>77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.

positive: COVID‐19: what if the brain had a role in causing the deaths? In the last few weeks Italy first, and then several other countries across the world, have been swept up by the deadly wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the illness named COVID-19, from the acronym CO (corona) VI (virus) D (disease) and 19 (year of the virus identification). The medical community is working day and night to assist affected people and experts in communicable diseases are striving in multiple ways to understand the progression of events leading to the lethal respiratory syndrome.

positive: Maternal death due to COVID-19 BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: 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 multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact 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, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.

positive: 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.

positive: Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.

positive: Higher Obesity Trends Among African Americans Are Associated with Increased Mortality in Infected COVID-19 Patients Within the City of Detroit As the city of Detroit raids itself of deaths by shifting from homicides, COVID-19 infection continues to harrow the city with more deaths. From March 19 to May 15, more Detroiters died in 2 months than were killed in 2 years of city homicides. African Americans or Blacks (highest-risk phenotypes) developing COVID-19 infection are more likely to die disproportionately. The confluence of diabetes, hypertension, cardiovascular disease, and the higher prevalence of obesity among Blacks have provided the needed environment for viruses like COVID-19 to thrive and cause serious infections. The purpose of this study is to connect mortality rates from COVID-19 infection to increasing obesity trends among African Americans within the city of Detroit. Statistical analyses were conducted using SPSS ver. 23. Results showed that the highest mortality rates among African Americans occurred more in the obese individuals infected with COVID-19 in the city of Detroit. Out of 1930 deaths from COVID-19 infections, 733 deaths were due to obesity alone in patients without reported comorbid conditions like diabetes, hypertension, and cardiovascular disease. Mortality rate for both male and female African Americans amounted to a total of 11.9%. Thirty-eight percent of reported COVID-19-infected African Americans were obese. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00385-y) contains supplementary material, which is available to authorized users.

positive: Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China OBJECTIVES: 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 radiological 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. RESULTS: 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, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. CONCLUSIONS: The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.

positive: Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

positive: Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of Valcamonica, Italy Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.

positive: Initial evidence of higher morbidity and mortality due to SARS-CoV-2 in regions with lower air quality COVID-19 has spread in all continents in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical expansion of the infection and correlate it with the annual indexes of air quality observed from the Sentinel-5 satellite orbiting around China, Italy and the U.S.A. Controlling for population size, we find more viral infections in those areas afflicted by Carbon Monoxide (CO) and Nitrogen Dioxide (NO2). Higher mortality was also correlated with poor air quality, namely with high PM2.5, CO and NO2 values. In Italy, the correspondence between poor air quality and SARS-CoV-2 appearance and induced mortality was the starkest. Similar to smoking, people living in polluted areas are more vulnerable to SARS-CoV-2 infections and induced mortality. This further suggests the detrimental impact climate change will have on the trajectory of future epidemics.

positive: COVID-19 update: Covid-19-associated coagulopathy

positive: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary. The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.

positive: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection 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 â¼2%, 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.

positive: Commentary: What is the relationship between Covid-19 and cardiovascular disease?

positive: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to nearly 190 countries. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood lab profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.

positive: 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.

positive: Infectious Atypical Pneumonia Infectious atypical pneumonia, also known as severe acute respiratory syndrome (SARS), is an acute respiratory infectious disease caused by SARS coronavirus (SARS-CoV). Clinically, it is characterized by fever, headache, muscular soreness, fatigue, dry cough rarely with phlegm, and diarrhea. Most patients experience accompanying pneumonia. In severe cases, the conditions may develop into acute lung injury, acute respiratory distress syndrome (ARDS), or even multiple organ failure that causes death. In China, SARS has been legally listed as one of the class B infectious diseases but is managed as class A infectious diseases, like anthrax and human infection of avian influenza.

positive: COVID-19 autopsy in people who died in community settings: the first series Here, we report the pathological findings of nine complete autopsies of individuals who died in community settings in the UK, three of which were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three tested negative for SARS-CoV-2 but are likely false negatives, and three died of other respiratory infections. Autopsy revealed firm, consolidated lungs or lobar pneumonia. Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space. This series is the first in the world to describe autopsy findings in individuals dying suddenly in the community, not previously known to have COVID-19 infection, and the first autopsy series in the UK. During a time when testing in the UK is currently primarily offered to patients in hospital or symptomatic key workers, with limited testing available in community settings, it highlights the importance of testing for COVID-19 at autopsy. Two deaths occurred in care homes where a diagnosis of COVID-19 allowed the health protection team to provide support in that 'closed setting' to reduce the risks of onward transmission. This work highlights the need for frequent COVID-19 testing in the management of patients in community settings. Comprehensive virology and microbiology assessment is pivotal to correctly identify the cause of death, including those due to COVID-19 infection, and to derive accurate death statistics.

positive: Coronavirus Disease-19: The First 7,755 Cases in the Republic of Korea We report the first 7,755 patients with confirmed COVID-19 in Korea as of March 12(th), 2020. A total of 66 deaths have been recorded, giving a case fatality proportion of 0.9%. Older people, and those with comorbidities were at a higher risk of a fatal outcome. The highest number of cases of COVID-19 were in Daegu, followed by Gyeongbuk. This summary may help to understand the disease dynamics in the early phase of the COVID-19 outbreaks, and may therefore, guide future public health measures.

positive: [Comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease 2019]. Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) shared similar pathogenetic, clinical and pathological features. Fever and cough were the most common symptoms of both diseases, while myalgia and diarrhea were less common in patients with COVID-19. Acute respiratory distress syndrome (ARDS) was the most severe pulmonary complication that caused high mortality rate. Histologically, diffuse alveolar damage (DAD) was the most characteristic finding in non-survivors with either SARS or COVID-19. Cases of patients died less than 10~14 days of disease duration demonstrated acute-phase DAD, while cases beyond 10~14 days of disease duration exhibited organizing-phase DAD in SARS. Meanwhile, organization and fibrosis were usually accompanied by exudation. Coronavirus was mostly detected in pneumocytes, while less in macrophages and bronchiolar epithelial cells. Hemorrhagic necrosis and lymphocytes depletion were found in lymph nodes and spleen in both SARS and COVID-19, indicating a pathological basis of lymphocytopenia. Thrombosis was commonly observed in small vessels and microvascular in lungs accompanying DAD. Microthrombosis was also found in extrapulmonary organs in COVID-19, that was less reported in SARS. Damages in multiple extrapulmonary organs were observed, but coronavirus was not detected in some of those organs, might indicating an alternative mechanism beyond viral infection, such as hypoxemia, ischemia and cytokine storm induced immunological injury. Diffuse alveolar damage due to viral infection and immunological injury, as well as multi-organ dysfunction and extensive microthrombus formation, brought huge challenge to the management of patients with severe SARS or COVID-19.

positive: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19–positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

positive: SARS – Pandemie und Emerging Disease The SARS-epidemic of 2002/2003 with worldwide 8.096 cases and 774 fatalities was the first pandemia of the 21(st) century. SARS, the severe acute respiratory syndrome, arose in southern China and spread from Southeast-Asia finally over all five continents. It caused heavy pneumonia with pulmonal failure and enteric involvement in man. The causative agent was a novel coronavirus (SARS-CoV), which was transmitted from bats to small carnivores and from them to man. The mutations of the viral receptor gene thus allowed the infection of man and the transmission from man to man. The SARS-pandemia can therefore be regarded as a model of an emerging disease.

positive: 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.

positive: Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. BACKGROUND Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS In patients who died from Covid-19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth - predominantly through a mechanism of intussusceptive angiogenesis - was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.).

positive: Unknown unknowns - COVID-19 and potential global mortality COVID-19 (SARS-CoV-2) is currently a global pandemic. This paper will attempt to estimate global infection rates and potential resultant mortality in the absence of effective treatment and/or vaccination. Calculations are based on World Health Organisation data from Wuhan in China: 14% of infected cases are severe, 5% require intensive care and 4% die. Estimated infection rates and mortality rates at the level of continents and some individual countries (when these are of sufficient size) are tabulated. This pandemic may cause close to half a billion deaths, i.e. 6% of the global population - and potentially more. At the risk of sounding sensational, but with a sober sense of realism, healthcare risks being plunged into the Middle-Ages if the public do not do their part. Infection cannot occur in the absence of contact. The only way to mitigate these numbers is to apply social distancing and take the standard precautions so frequently reiterated by Public Health: hand washing, avoid touching the face and so on. These measures are crucial as the human cost is going to be unthinkable even in the best-case scenarios that epidemiologists are modelling.

positive: Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (-3.7 g/L, 95% CI, -5.3 to -2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.

positive: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology. The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.

positive: The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.

positive: 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.

positive: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis Abstract Introduction We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals. In answering questions raised regarding our study, we updated our database and repeated all analyses. Methods We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first. Results We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%). The median follow-up duration increased from 7 to 14 days. All patients received pharmacological thromboprophylaxis. The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41–57%). The majority of thrombotic events were PE (65/75; 87%). In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091–0.92). Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4–12). Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35–1.8). Conclusion In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

positive: Reduction of lymphocyte at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study Background and objective: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has been pandemic worldwide. Several reports observed a reduction of lymphocytes among COVID-19 patients. However, clinical significance of lymphocyte reduction in COVID-19 patients remains unclear. The objective of this study was to analyze the association between lymphocyte reduction at early stage and the prognosis of COVID-19 patients. Methods: All 192 hospitalized patients with COVID-19 were enrolled. Electronic medical records, including demographic data, clinical characteristics, comorbidities and exposure history, were collected. Biochemical indexes on admission and chest computed tomography (CT) were detected. Patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphocyte reduction among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among more than seventy-year-old patients than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphocyte reduction. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphocyte reduction. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphocyte reduction. Moreover, TBIL and DBIL, two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphocyte reduction. Among 84 COVID-19 patients with lymphocyte reduction, 32.1% died. Fatality rate was obviously higher in COVID-19 patients with lymphocyte reduction than those with normal lymphocyte (RR=5.789, P<0.001). Conclusion: Older COVID-19 patients are more susceptible to lymphocyte reduction. Lymphocyte reduction at early stage aggravates the severity of multiple organ injuries and elevates death risk of COVID-19 patients.

positive: A Multicentre Study of 2019 Novel Coronavirus Disease Outcomes of Cancer Patients in Wuhan, China Background: At present, there is a global pandemic of coronavirus disease 2019 (COVID-19) pneumonia. Two previous case series from China have suggested that cancer patients are at a higher risk of COVID-19 pneumonia, but the reports were limited by small numbers and few clinical information. Objective: To study clinical characteristics and outcomes of cancer patients infected with COVID-19. Design: Retrospective study. Setting: Four designated COVID-16 hospitals in Wuhan, Hubei province, China. Participants: Medical records of 67 cancer patients admitted to hospitals between Jan 5, 2020 to Feb 18, 2020 were included. Measurements: Demographic, clinical, laboratory, radiological and treatment data were collected. Survival data of the cohort was cut-off on Mar 10, 2020. Results: Of the 67 patients (median age: 66 years), the median age of patients who had severe illness was older than that of patients who had mild symptoms (P<0.001). Forty-three (64.2%) patients had other concurrent chronic diseases, and the proportion of severe patients had co-morbidities was higher than patients with mild disease (P=0.004). Twenty-three (34.3%) patients were still at the anticancer treatment phase, but no tumour progression and recurrence was observed for all the patients during the treatment of COVID-19 pneumonia. About 70% of these patients had fever (n=53, 79.1%) and/or cough (n=50, 74.6%). Lymphocytopenia was the main laboratory finding accompanying increased C-reactive protein and procalcitonin in cancer patients, especially in severe cases. By Mar 10, 2020, 18 (26.9%) patients died from COVID-19, and 39 (58.2%) patients have been discharged. The median age of survivors was younger than that of deaths (P=0.014). Lung cancer (n=15, 22.4%) with COVID-19 was the most common cancer type and accounted for the highest proportion COVID-19 resulted deaths (33.3%, 5/15). We observed a tendency that patients at the follow-up phase had a better prognosis than that at anticancer treatment phase (P=0.095). Limitation: This is a retrospective study with only 67 cases from four hospitals. And some specific clinical information was insufficient. Conclusion: This study showed COVID-19 patients with cancer seem to have a higher proportion of severe cases and poorer prognosis. The tendency of poor prognosis was more obvious in patients at anticancer treatment phase. We should pay more intensive attentions to cancer patients infected with COVID-19.

positive: Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).

positive: Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.

positive: Association of BCG vaccination policy with prevalence and mortality of COVID-19 There is some evidence that tuberculosis vaccine bacillus Calmette-Guérin (BCG) has non-specific beneficial effects against non-related infections. Here, we examined the possible association between BCG vaccination with prevalence and mortality by COVID-19 by using publicly available data of COVID-19 in 199 countries/regions and the BCG World Atlas. By using linear regression modeling, we found that the number of total cases and deaths per one million population were significantly associated with the country's policy concerning BCG vaccine administration. The amount of variance in cases and deaths explained by BCG vaccination policy ranged between 12.5% and 38%. Importantly, this effect remained significant after controlling for the country's life expectancy and the average temperature in February and March 2020, which themselves are significantly correlated with the cases and deaths indices, respectively. By contrast, the ratio between deaths and cases was weakly affected. This latter outcome suggested that BCG vaccination may have hindered the overall spread of the virus or progression of the disease rather than reducing mortality rates (i.e., deaths/cases ratio). Finally, by roughly dividing countries into three categories showing high, middle, or low growth rate of the cases, we found a highly significant difference between the slope categories among the BCG groups, suggesting that the time since the onset of the spread of the virus was not a major confounding factor. While this study potentially suffers from a number of unknown confounding factors, these associations support the idea that BCG vaccination may provide protection against SARS-CoV-2, which, together with its proven safety, encourages consideration of further detailed epidemiological studies, large-scale clinical trials on the efficacy of this vaccine on COVID-19, and/or re-introduction of BCG vaccination practice in the countries which are currently devoid of the practice.

positive: 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.

positive: A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm) The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.

positive: Clinicolaboratory study of 25 fatal cases of COVID-19 in Wuhan

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: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 µg/mL (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 µg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

positive: Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan

positive: Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19): Pooled analysis of early reports

positive: Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement Since the new coronavirus SARS (SARS-CoV2) has emerged from china, the infection (COVID-19) has affected many countries and led to many deaths worldwide. Like SARS-CoV, ACE2 as a functional receptor for SARS-CoV2 is essential for virus to entry to the cell. ACE2 is a part of RAS which is expressed in several organs that opposes the AngII functions by converting Ang II to Ang (1-7), the one with vasodilation effects. The death rate of COVID-19 is estimated about 3.4%, however, some comorbid conditions like underlying cardiovascular disease, hypertension, and diabetes increase the risk of mortality. In addition, cardiovascular involvement by SARS-CoV2 could be direct through either ACE2 receptors which are expressed tremendously in heart, or by the surge of different cytokines or by ARDS-induced hypoxia. Traditional risk factors could aggravate the process of COVID-19 infection that urges the triage of these high risk patients for SARS-CoV2. Currently, there is no effective, proven treatment or vaccination for COVID-19, but many investigators are struggling to find a treatment strategy as soon as possible. Some potential medications like chloroquine by itself or in combination with azithromycin, and some protease inhibitors used for the treatment of COVID-19 have cardiovascular adverse effects that should be kept in mind in order to close monitor of the patients receiving these medications.

positive: Influence of COVID-19 on Cerebrovascular Disease and its Possible Mechanism The global spread of COVID-19 has caused a substantial societal burden and become a major global public health issue. The COVID-19 elderly population with hypertension, diabetes, cardiovascular, and cerebrovascular diseases are at risk. Mortality rates are highest in these individuals if infected with COVID-19. Although the lungs are the main organs involved in acute respiratory distress syndrome caused by COVID-19 infection, COVID-19 triggers inflammatory and immune mechanisms, inducing a “cytokine storm” that aggravates disease progression and may lead to death. Presently, effective drugs are lacking, although current studies have confirmed that drugs with therapeutic potential include redaciclovir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. Currently, the most reasonable and effective way to prevent COVID-19 is to control the source of infection, terminate routes of transmission, and protect susceptible populations. With the rise of COVID-19 in China and worldwide, further prevention, diagnosis, and treatment measures are a critical unmet need. Cerebrovascular disease has high incidence, disability rate, and fatality rate. COVID-19 patient outcomes may also be complicated with acute stroke. This paper summarizes the influence of COVID-19 on cerebrovascular disease and discusses possible pathophysiological mechanisms to provide new angles for the prevention and diagnosis of this disease.

positive: Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study Abstract Background In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. Methods In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation. Results Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. Conclusions Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.

positive: Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment.

positive: 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.

positive: COVID-19 in Immunocompromised Hosts: What We Know So Far The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features and outcomes of COVID-19 among immunosuppressed patients, who are at presumed risk for more severe disease but who may also have decreased detrimental inflammatory responses, are not well characterized. We review the existing literature on COVID-19 among immunocompromised populations ranging from cancer patients and solid organ transplant recipients to patients with HIV and those receiving immunomodulatory therapy for autoimmune disease. Patients with malignancy and solid organ transplant recipients may be at increased risk of severe COVID-19 disease and death whereas for those with other types of immunocompromise, current evidence is less clear. Overall, further prospective, controlled studies are needed to determine the attributable risk of immunocompromising conditions and therapies on COVID-19 disease prognosis.

positive: African American COVID-19 Mortality: A Sentinel Event

positive: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (≥ 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population ≥ 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = −0.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.

positive: SARS‐CoV‐2: What do we know so far? We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and patients with underlying comorbidities are at a higher risk of death. We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 manifests as dry cough, frequent fevers and in severe cases pneumonia.

positive: An inflammatory cytokine signature helps predict COVID-19 severity and death The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-, and IL-1{beta} in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF- levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF- serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF- levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF- levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

positive: Estimation of risk factors for COVID-19 mortality - preliminary results Since late December 2019 a new epidemic outbreak has emerged from Whuhan, China. Rapidly the new coronavirus has spread worldwide. China CDC has reported results of a descriptive exploratory analysis of all cases diagnosed until the 11th February 2020, presenting the epidemiologic curves and geo-temporal spread of COVID-19 along with case fatality rate according to some baseline characteristics, such as age, gender and several well-established high prevalence comorbidities. Despite this, we intend to increase even further the predictive value of that manuscript by presenting the odds ratio for mortality due to COVID-19 adjusted for the presence of those comorbidities and baseline characteristics such as age and gender. Besides, we present a way to determine the risk of each particular patient, given his characteristics. We found that age is the variable that presents higher risk of COVID-19 mortality, where 60 or older patients have an OR = 18.8161 (CI95%[7.1997; 41.5517]). Regarding comorbidities, cardiovascular disease appears to be the riskiest (OR=12.8328 CI95%[10.2736; 15.8643], along with chronic respiratory disease (OR=7.7925 CI95%[5.5446; 10.4319]). Males are more likely to die from COVID-19 (OR=1.8518 (CI95%[1.5996; 2.1270]). Some limitations such as the lack of information about the correct prevalence of gender per age or about comorbidities per age and gender or the assumption of independence between risk factors are expected to have a small impact on results. A final point of paramount importance is that the equation presented here can be used to determine the probability of dying from COVID-19 for a particular patient, given its age interval, gender and comorbidities associated.

positive: Coronaviruses pathogenesis, comorbidities and multi-organ damage – A review Human coronaviruses, especially COVID-19, is an emerging pandemic infectious disease with high morbidity and mortality. Coronaviruses are associated with comorbidities, along with the symptoms of it. SARS-CoV-2 is one of the highly pathogenic coronaviruses that causes a high death rate compared to the SARS-CoV and MERS. In this review, we focused on the mechanism of coronavirus with comorbidities and impairment in multi-organ function. The main dysfunction upon coronavirus infection is damage to alveolar and acute respiratory failure. It is associated with the other organ damage such as cardiovascular risk via an increased level of hypertension through ACE2, gastrointestinal dysfunction, chronic kidney disease, diabetes mellitus, liver dysfunction, lung injury, CNS risk, ocular risks such as chemosis, conjunctivitis, and conjunctival hyperemia, cancer risk, venous thromboembolism, tuberculosis, aging, and cardiovascular dysfunction and reproductive risk. Along with this, we have discussed the immunopathology and coronaviruses at a molecular level and therapeutic approaches for the coronavirus infection. The comorbidities and multi-organ failure of COVID-19 have been explained at a molecular level along with the base of the SARS-CoV and MERS-CoV. This review would help us to understand the comorbidities associated with the coronaviruses with multi-organ damage.

positive: The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.

positive: Causes of Death and Comorbidities in Patients with COVID-19 Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has caused several hundreds of thousands of deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of comorbidities to death yet is missing. Here, we report autopsy findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as the most immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

positive: Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19 Background The illness progress of partial patient of COVID-19 is rapid and the mortality rate is high.we aim to describe the clinical features in death cases with COVID-19. Methods In this single center, observational study, We recruited all Death Cases with COVID-19 from Dec 30, 2019 to Feb 16, 2020 in Intensive care unit of Wuhan Jinyintan Hospital.Demographics, basic diseases, X-ray/CT results, possible therapy strategies and test results when their entrance into admission, ICU and 48 h before death were collected and analyzed. Results This study involved 101 COVID-19 dead cases in Intensive care unit of Wuhan Jinyintan Hospital.47 patients went directly to the ICU because of critical condition, and 54 patients were transferred to ICU with aggravated condition.57 (56.44%) were laboratory confirmed by RT-PCR, and 44 (43.6%) were consistent with clinical diagnostic criteria.The cases included 64 males and 37 females with average age of 65.46 years (SD 9.74). The blood type distribution was significantly different, with type A 44.44%, type B 29.29%, type AB 8.08% and type O 18.19%.The clinical manifestations of new coronavirus pneumonia are non-specific,the common symptom was fever (91 [90.10%] of 101 patients),Cough (69[68.32%]) and dyspnea (75[74.26%]). Neutrophils, PCT, CRP,IL-6,D-dimer gradually increased as time went on.Myocardial enzymes were abnormal in most patients at admission,with the progress of the disease, myocardial damage indicators were significantly increased.61(60.40%) used antiviral drugs,59(58.42%) used glucocorticoids, 63.37% used intravenous immunoglobulins, and 44.55% used thymosin preparations. All patients received antibiotic treatment, 63(62.38%) used restricted antibiotics, 23(22.78%) used antifungal drugs.84(83.17%) used non-invasive ventilator or high-flow oxygen therapy equipment, and 76.24% used invasive mechanical ventilation. 7 patients were treated with ECMO and 8 patients were treated with CRRT.The median time from ARDS to invasive mechanical ventilation was 3.00 days(IQR 0.00-6.00). The duration of invasive mechanical ventilation was 5 days (IQR2.00-8.00). Conclusions Critical COVID-19 can cause fatal respiratory distress syndrome and multiple organ failure with high mortality rate. Heart may be the earliest damaged organ except the lungs. Secondary infection in the later period is worthy of attention.

positive: Prognostic Value of Cardiovascular Biomarkers in COVID-19: A Review In early December 2019, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China. As of May 10th, 2020, a total of over 4 million COVID-19 cases and 280,000 deaths have been reported globally, reflecting the raised infectivity and severity of this virus. Amongst hospitalised COVID-19 patients, there is a high prevalence of established cardiovascular disease (CVD). There is evidence showing that COVID-19 may exacerbate cardiovascular risk factors and preexisting CVD or may lead to cardiovascular complications. With intensive care units operating at maximum capacity and such staggering mortality rates reported, it is imperative during this time-sensitive COVID-19 outbreak to identify patients with an increased risk of adverse outcomes and/or myocardial injury. Preliminary findings from COVID-19 studies have shown the association of biomarkers of acute cardiac injury and coagulation with worse prognosis. While these biomarkers are recognised for CVD, there is emerging prospect that they may aid prognosis in COVID-19, especially in patients with cardiovascular comorbidities or risk factors that predispose to worse outcomes. Consequently, the aim of this review is to identify cardiovascular prognostic factors associated with morbidity and mortality in COVID-19 and to highlight considerations for incorporating laboratory testing of biomarkers of cardiovascular performance in COVID-19 to optimise outcomes.

positive: Clinical characteristics of Coronavirus Disease 2019 (COVID-19) patients in Kuwait Abstract Background: In early December 2019, the first clusters of Coronavirus Disease 2019 (COVID-19) were identified in Wuhan, China and attributed to a novel coronavirus, now known as Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2). Kuwait reported its first cases of COVID-19 on February 24th 2020 and since then the number of cases has been increasing rapidly. Methods and Findings: This is a retrospective single-center study of consecutive 417 COVID-19 patients admitted to Jaber Al-Ahmad hospital between 24/2/2020 and 24/5/2020. The mean age of cohort was 45.35 years (S.D. 17.16) and 62.8% of cases were males. Patients were divided into four groups; Asymptomatic group, symptomatic group with mild form of the disease, ICU survivors and ICU death. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild symptoms, 5.3% were admitted to ICU and recovered and 14.4% died. Mean age of ICU patients was 53.61 years (S.D. 13.43). Comorbidities were more prevalent in ICU death group when compared to other groups (p<0.05) including Diabetes (40%), Hypertension (46.7%), Asthma (20.3%) and cardiovascular disease (21.7%). Blood biochemistry analysis showed that ICU death group had a characteristic abnormal pattern of certain markers upon admission in the ICU. Including significantly high WBC and neutrophil counts (P<0.05) and prolonged Prothrombin Time (PT) and activated partial thromboplastin time (APTT) (P<0.05). D-dimer, C-reactive protein and Procalcitonin (PCT) showed significantly high levels in ICU admissions and in ICU death group in particular (P<0.05). Kidney injury complications were reported in 65% of ICU death group (P<0.05) which also showed significantly elevated urea levels (P<0.05). We also reported rapid deteriorating kidney function (eGFR) in ICU death cases during ICU stay until the outcome was reached. Conclusions: In this single-center study of 417 COVID19 patients in Kuwait. The disease showed varying degree of severity ranging from asymptomatic status to death. Our comprehensive laboratory analysis revealed distinct abnormal patterns of markers that are associated with poor prognosis. Our dynamic profiling of eGFR in COVID-19 ICU patients highlight potential role of renal markers in forecasting disease outcome and perhaps identify patients at risk of poor outcome.

positive: D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19 BACKGROUND: The outbreak of the coronavirus disease 2019 (Covid-19) has shown a global spreading trend. Early and effective predictors of clinical outcomes are urgently needed to improve management of Covid-19 patients. OBJECTIVE: The aim of the present study was to evaluate whether elevated D-dimer levels could predict mortality in patients with Covid-19. METHODS: Patients with laboratory confirmed Covid-19 were retrospective enrolled in Wuhan Asia General Hospital from January 12, 2020, to March 15, 2020. D-dimer levels on admission and death events were collected to calculate the optimum cutoff using receiver operating characteristic curves. According to the cutoff, the subjects were divided into two groups. Then the in-hospital mortality between two groups were compared to assess the predictive value of D-dimer level. RESULTS: A total of 343 eligible patients were enrolled in the study. The optimum cutoff value of D-dimer to predict in-hospital mortality was 2.0 µg/mL with a sensitivity of 92.3% and a specificity of 83.3%. There were 67 patients with D-dimer ≥2.0 µg/mL, and 267 patients with D-dimer <2.0 µg/mL on admission. 13 deaths occurred during hospitalization. Patients with D-dimer levels ≥2.0 µg/mL had a higher incidence of mortality when comparing with those who with D-dimer levels <2.0 µg/mL (12/67 vs 1/267, P < .001; hazard ratio, 51.5; 95% confidence interval, 12.9-206.7). CONCLUSIONS: D-dimer on admission greater than 2.0 µg/mL (fourfold increase) could effectively predict in-hospital mortality in patients with Covid-19, which indicated D-dimer could be an early and helpful marker to improve management of Covid-19 patients. (Chinese Clinical Trial Registry: ChiCTR2000031428).

positive: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 - United States, February 12-March 28, 2020 On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

positive: COVID-19 outbreak impact in Spain: A role for tobacco smoking?

positive: 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.

positive: Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System Patients with cancer are presumed to be at increased risk from COVID-19 infection–related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19–positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. SIGNIFICANCE: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. This article is highlighted in the In This Issue feature, p. 890

positive: Impact of blood analysis and immune function on the prognosis of patients with COVID-19 Introduction: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with 2019-coronavirus infected disease (COVID-19). Methods: Records were reviewed of 85 patients with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital mortality at 28 days. Results: Fourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non-survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO2/FiO2, CD3+ count and CD4+ count. The percentage of neutrophil count > 6.3*109/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE > 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts. Conclusions: For patients with COVID-19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. A high neutrophil count is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention.

positive: Cancer inpatient with COVID-19: a report from the Brazilian National Cancer Institute Brazil has been recording a frightening exponential curve of confirmed cases of SARS-CoV-2 infection. Cancer patients with COVID-19 are likely to have a greater risk of complications and death. A retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR method. The mean age was 55.3 years (SD 21.1). The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. By multivariate analysis, cases with admission due to symptoms of COVID-19 (p = 0.027) and with two or more metastatic sites (p <0.001) showed a higher risk of COVID-19-specific death. This is the first study in a cohort of Brazilian cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high. Our data prompts urgent and effective public policies for this group of especially vulnerable patients.

positive: Hypoxia in acute cardiac injury of coronavirus disease 2019: lesson learned from pathological studies

positive: Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality 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.

positive: 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.

positive: Geographic Differences in COVID-19 Cases, Deaths, and Incidence - United States, February 12-April 7, 2020 Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States. Cumulative COVID-19 incidence varied substantially by jurisdiction, ranging from 20.6 cases per 100,000 in Minnesota to 915.3 in NYC. On April 7, national case doubling time was approximately 6.5 days, although this ranged from 5.5 to 8.0 days in the 10 jurisdictions reporting the most cases. Absolute change in cumulative incidence during March 31-April 7 also varied widely, ranging from an increase of 8.3 cases per 100,000 in Minnesota to 418.0 in NYC. Geographic differences in numbers of COVID-19 cases and deaths, cumulative incidence, and changes in incidence likely reflect a combination of jurisdiction-specific epidemiologic and population-level factors, including 1) the timing of COVID-19 introductions; 2) population density; 3) age distribution and prevalence of underlying medical conditions among COVID-19 patients (1-3); 4) the timing and extent of community mitigation measures; 5) diagnostic testing capacity; and 6) public health reporting practices. Monitoring jurisdiction-level numbers of COVID-19 cases, deaths, and changes in incidence is critical for understanding community risk and making decisions about community mitigation, including social distancing, and strategic health care resource allocation.

positive: Death from Covid-19 of 23 Health Care Workers in China

positive: COVID-19 and Dialysis Units: What Do We Know Now and What Should We Do?

positive: Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase "acute respiratory distress syndrome" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.

positive: 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.

positive: 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.

positive: Implications of the reverse associations between obesity prevalence and coronavirus disease (COVID-19) cases and related deaths in the United States The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was most recently discovered, quickly evolved into a global pandemic. Studies suggested that obesity was a major risk factor for its hospitalization and severity of symptoms. This study investigated the associations between obesity prevalence with overall COVID-19 cases and related deaths across states in the United States. General regression and Chi-square tests were used to examine those associations. The analyses indicated that obesity prevalence (%) across states were negatively associated with COVID-19 cases (p = 0.0448) and related deaths (p = 0.0181), with a decrease of 158 cases/100K population and 13 deaths/100K for every 5% increase of the obesity prevalence. When the states were divided based on the median of obesity prevalence (30.9%) into a group of states with low obesity prevalence and a group with high obesity prevalence, both the cases (671 vs 416 cases/100k population) and deaths (39 vs 21 deaths/100k population) were significantly different (p < 0.001) across groups. These findings provided important information for the relationship between the dual pandemic threats of obesity and COVID-19. These results should not currently be considered as an indication that obesity is a protective factor for COVID-19, and would rather be used as a warning of the public advice that obese people is more vulnerable to COVID-19 infection, which may lead to a false safety message probably given to people with normal body weight.

positive: COVID-19: is fibrosis the killer? COVID-19 is a respiratory disease A recent report in Lancet examined, retrospectively, 137 patients with COVD-19 Patients that died had elevated IL-6 levels and acute respiratory distress syndrome These data have obvious implications for how to control mortality in COVID-19

positive: Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. Results: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 10(9)/L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. Conclusions: Baseline platelet levels and changes were associated with subsequent mortality. Monitoring platelets during hospitalization may be important in the prognosis of patients with coronavirus disease in 2019.

positive: 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.

positive: Pathological findings of COVID-19 associated with acute respiratory distress syndrome

positive: A novel cohort analysis approach to determining the case fatality rate of COVID-19 and other infectious diseases As the Coronavirus contagion develops, it is increasingly important to understand the dynamics of the disease. Its severity is best described by two parameters: its ability to spread and its lethality. Here, we combine a mathematical model with a cohort analysis approach to determine the range of case fatality rates (CFR). We use a logistical function to describe the exponential growth and subsequent flattening of COVID-19 CFR that depends on three parameters: the final CFR (L), the CFR growth rate (k), and the onset-to-death interval (t0). Using the logistic model with specific parameters (L, k, and t0), we calculate the number of deaths each day for each cohort. We build an objective function that minimizes the root mean square error between the actual and predicted values of cumulative deaths and run multiple simulations by altering the three parameters. Using all of these values, we find out which set of parameters returns the lowest error when compared to the number of actual deaths. We were able to predict the CFR much closer to reality at all stages of the viral outbreak compared to traditional methods. This model can be used far more effectively than current models to estimate the CFR during an outbreak, allowing for better planning. The model can also help us better understand the impact of individual interventions on the CFR. With much better data collection and labeling, we should be able to improve our predictive power even further.

positive: Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

positive: 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.

positive: COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death? Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.

positive: Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages Background: Information about the clinical characteristics and mortality of patients with coronavirus disease 2019 at different ages is limited. Results: The older group had more patients with dyspnea and fewer patients with fever and muscle pain. Older patients had more underlying diseases, secondary infection, myocardial injury, renal dysfunction, coagulation dysfunction, and immune dysfunction on admission. More older patients received immunoglobulin therapy and mechanical ventilation. The proportions of patients with multiple organ injuries, critically ill patients and death increased significantly with age. The older groups had higher cumulative death risk than the younger group. Hypertension, cerebrovascular disease, comorbidities, acute cardiac injury, shock and complications are independent predictors of death. Conclusions: The symptoms of the elderly patients were more atypical, with more comorbidities, secondary infection, organ injuries, immune dysfunction and a higher risk of critical illness. Older age was an important risk factor for mortality. Methods: 1000 patients diagnosed with coronavirus disease 2019 from January 1, 2020 to February 14, 2020 were enrolled. According to age, patients were divided into group 1 (<60 years old), group 2 (60-74 years old) and group 3 (≥75 years old). The clinical symptoms, first laboratory results, CT findings, organ injuries, disease severity and mortality were analyzed.

positive: 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.

positive: Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection BACKGROUND The outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODS We conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) and in situ expression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM). RESULTS 27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22% vs 24.19%, p< 0.001; 69.57% vs 11.29%, p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses- like particles are visible in the kidneys. Viral infection not only induces CD68+ macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules. CONCLUSIONS SARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+ macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.

positive: Encountering COVID-19 as Endocrinologists. The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.

positive: 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.

positive: Who is dying from Covid-19 in the United Kingdom? A review of cremation authorisations from a single South Wales' crematorium. Abstract Background: Covid 19 is pandemic in the UK. To date only studies in the UK on hospital deaths have been published in the peer reviewed literature. Legal requirements for cremation in England and Wales require the collection of information that can be used to improve understanding of Covid 19 deaths in both hospital and community settings. Aim: To document demographic and clinical characteristics, including likely place of infection, of individuals dying of Covid 19 to inform public health policy Design: A comprehensive case series of deaths from Covid 19 between 6 April and 30 May. Setting: A crematorium in South Wales Participants: Individuals for whom an application was made for cremation. Main outcome measures: Age, sex, date and place of death, occupation, comorbidities, where infection acquired. Results: Of 752 cremations, 215(28.6%) were Covid-19 of which 115 (53.5%) were male and 100 (46.5%) female. The median age was 82 years, with the youngest patient being 47 years and the oldest 103 years. Over half the deaths (121/215: 56.3%) were over 80 years. Males odds of dying in hospital, rather than the community were 1.96 times that of females (95% Confidence Intervals (CI) 1.03 -3.74, p=0.054) despite being of similar age and having a similar number of comorbidities. Only 21(9.8%) of 215 patients had no comorbidities recorded. Patients dying in nursing homes were significantly older than those dying in hospital(median 88y (IQ range 82-93y) v 80y (IQ range 71-87y): p<0.0001). Patients dying in hospital had significantly more comorbidities than those dying in nursing homes (median 2: IQ range 1-3 v. 1: IQ range 1-2: p <0.001). Conclusions: In a representative series, comprising both hospital and community deaths, persons over 80 with an average 2 comorbidities predominated. Although men and women were represented in similar proportions, men were more likely to die in hospital. Over half the infections were acquired in either hospitals or nursing and residential homes with implications for the management of the pandemic, historically and in the future.

positive: 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.

positive: Cytokine storm induced by SARS-CoV-2 Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.

positive: Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.

positive: Scoring systems for predicting mortality for severe patients with COVID-19 BACKGROUND: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, especially in patients with severe COVID-19. This analysis aimed to explore risk factors for mortality of severe COVID-19, and establish a scoring system to predict in-hospital deaths. METHODS: Patients with COVID-19 were retrospectively analyzed and clinical characteristics were compared. LASSO regression as well as multivariable analysis were used to screen variables and establish prediction model. FINDINGS: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66•0 years while it was 73•0 years in non-survivors. Patients aged 60–75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20–30 days. No differences were observed of antibody levels between severe and non-severe patients. About 60.2% of severe patients had complications. Among acute myocardial injury (AMI), acute kidney injury (AKI) and acute liver injury (ALI), the heart was the earliest injured organ, whereas the time from AKI to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariable analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established to divide patients into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P=0·264). Complications in low-risk and high-risk groups were significantly different (P<0·05). Use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P=0·036) and durations of disease by 7·5 days (P=0·012) compared with no corticosteroids. INTERPRETATION: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. FUNDING: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500).

positive: Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study OBJECTIVE: To describe outcomes of people admitted to hospital with coronavirus disease 2019 (covid-19) in the United States, and the clinical and laboratory characteristics associated with severity of illness. DESIGN: Prospective cohort study. SETTING: Single academic medical center in New York City and Long Island. PARTICIPANTS: 5279 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection between 1 March 2020 and 8 April 2020. The final date of follow up was 5 May 2020. MAIN OUTCOME MEASURES: Outcomes were admission to hospital, critical illness (intensive care, mechanical ventilation, discharge to hospice care, or death), and discharge to hospice care or death. Predictors included patient characteristics, medical history, vital signs, and laboratory results. Multivariable logistic regression was conducted to identify risk factors for adverse outcomes, and competing risk survival analysis for mortality. RESULTS: Of 11 544 people tested for SARS-Cov-2, 5566 (48.2%) were positive. After exclusions, 5279 were included. 2741 of these 5279 (51.9%) were admitted to hospital, of whom 1904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age, with an odds ratio of >2 for all age groups older than 44 years and 37.9 (95% confidence interval 26.1 to 56.0) for ages 75 years and older. Other risks were heart failure (4.4, 2.6 to 8.0), male sex (2.8, 2.4 to 3.2), chronic kidney disease (2.6, 1.9 to 3.6), and any increase in body mass index (BMI) (eg, for BMI >40: 2.5, 1.8 to 3.4). The strongest risks for critical illness besides age were associated with heart failure (1.9, 1.4 to 2.5), BMI >40 (1.5, 1.0 to 2.2), and male sex (1.5, 1.3 to 1.8). Admission oxygen saturation of <88% (3.7, 2.8 to 4.8), troponin level >1 (4.8, 2.1 to 10.9), C reactive protein level >200 (5.1, 2.8 to 9.2), and D-dimer level >2500 (3.9, 2.6 to 6.0) were, however, more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone. CONCLUSIONS: Age and comorbidities were found to be strong predictors of hospital admission and to a lesser extent of critical illness and mortality in people with covid-19; however, impairment of oxygen on admission and markers of inflammation were most strongly associated with critical illness and mortality. Outcomes seem to be improving over time, potentially suggesting improvements in care.

positive: Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.

positive: Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study. BACKGROUND In December, 2019, China, has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P= 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P< 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P< 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95%CI: 1.09, 8.21, P= 0.034), higher CRP levels (aRR: 1.02, 95%CI: 1.01, 1.03, P= 0.044), and lower lymphocyte (aRR: 0.82, 95%CI: 0.73, 0.93, P= 0.003) were associated with increased risk of death. CONCLUSIONS Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.

positive: High mortality in COVID‐19 patients with mild respiratory disease INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS‐CoV‐2, presenting with mild symptoms, and requiring hospitalization in a non‐intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non‐invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 10(3)/mm(3)) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in‐hospital mortality. CONCLUSIONS: In‐hospital mortality of patients with COVID‐19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID‐19.

positive: Real-time estimation and prediction of mortality caused by COVID-19 with patient information based algorithm The global COVID-19 outbreak is worrisome both for its high rate of spread, and the high case fatality rate reported by early studies and now in Italy. We report a new methodology, the Patient Information Based Algorithm (PIBA), for estimating the death rate of a disease in real-time using publicly available data collected during an outbreak. PIBA estimated the death rate based on data of the patients in Wuhan and then in other cities throughout China. The estimated days from hospital admission to death was 13 (standard deviation (SD), 6â¯days). The death rates based on PIBA were used to predict the daily numbers of deaths since the week of February 25, 2020, in China overall, Hubei province, Wuhan city, and the rest of the country except Hubei province. The death rate of COVID-19 ranges from 0.75% to 3% and may decrease in the future. The results showed that the real death numbers had fallen into the predicted ranges. In addition, using the preliminary data from China, the PIBA method was successfully used to estimate the death rate and predict the death numbers of the Korean population. In conclusion, PIBA can be used to efficiently estimate the death rate of a new infectious disease in real-time and to predict future deaths. The spread of 2019-nCoV and its case fatality rate may vary in regions with different climates and temperatures from Hubei and Wuhan. PIBA model can be built based on known information of early patients in different countries.

positive: Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients Higher rates of serious illness and death from coronavirus SARS-CoV-2 (COVID-19) infection among older people and those who have comorbidities suggest that age- and disease-related biological processes make such individuals more sensitive to environmental stress factors including infectious agents like coronavirus SARS-CoV-2. Specifically, impaired redox homeostasis and associated oxidative stress appear to be important biological processes that may account for increased individual susceptibility to diverse environmental insults. The aim of this Viewpoint is to justify (1) the crucial roles of glutathione in determining individual responsiveness to COVID-19 infection and disease pathogenesis and (2) the feasibility of using glutathione as a means for the treatment and prevention of COVID-19 illness. The hypothesis that glutathione deficiency is the most plausible explanation for serious manifestation and death in COVID-19 patients was proposed on the basis of an exhaustive literature analysis and observations. The hypothesis unravels the mysteries of epidemiological data on the risk factors determining serious manifestations of COVID-19 infection and the high risk of death and opens real opportunities for effective treatment and prevention of the disease.

positive: 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.

positive: Lymphopenia that may develop in patients treated with temozolomide and immune control check-point inhibitor may be a high risk for mortality during the COVID-19 outbreak As we know more about the clinical and laboratory features of COVID-19, which is now accepted as a pandemic, many questions have been raised about how to manage and monitor the treatment of cancer patients. It was determined that the incidence of lymphopenia increased in COVID-19 and there was a significant relationship between lymphopenia and mortality. This can be thought of as an unresponsive problem in how to maintain anti-cancer drugs that cause lymphopenia. This article was written for a hypothetical approach in cancer patients diagnosed with COVID-19 in order to be an idea of collecting data for treatment with anti-cancer drugs that cause lymphopenia.

positive: Covid-19 in Diabetes Patients in Ukraine: Lessons for Doctors and Patients World Health Organization recognized coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. The first case of COVID-19 in Ukraine was confirmed on 3 March 2020 in Chernivtsi and the first lethal case was reported on 13 March 2020. As of 22 April 2020 6592 cases of COVID-19 have been reported in Ukraine, among these cases 174 caused death (2.64% lethality), 467 patients (7.08% of cases) have recovered. The feature of COVID-19 pandemics in Ukraine is that the age of patients is lower (50-59 years old, 40-49 years old and 30-39 years old) than in China and other European countries. Another feature of COVID-19 epidemiology in Ukraine is that virus cause disease in women (56.0%) more often than in men (44.0%). But there are more male patients in other countries. Although there are more male deaths (51.7%) than female (48.3%) in Ukraine. Deaths have occurred in 30-49 years old patients (14%), in 50-69 years old patients (48%), in 70 years old and older patients (38%). 85% of all deaths were over 50 years of age. 79% of patients who died from COVID-19 had severe cardiovascular diseases, diabetes mellitus, neoplasms, renal diseases, respiratory disorders and obesity. In total, co-morbidities (one or several) have been cardiovascular diseases (74%), diabetes mellitus (22%), lungs diseases (9%), neoplasms (8%), renal diseases (7%). In this article we analyzed epidemiology and causes of negative influence of diabetes mellitus on COVID-19 progress in world and Ukraine. We also made recommendations on prophylaxis and patients treatment in cases of COVID-19 and diabetes mellitus co-morbidity.

positive: Impact of COVID-19 on the Cardiovascular System: A Review The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.

positive: Microvascular Disease Confers Additional Risk to COVID-19 Infection The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention. MVD And COVID Abstract The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) results in COVID-19 which can lead to severe illness and death. The majority of fatalities thus far in the pandemic have been attributed to pneumonia. The overall mortality risk reported as of March 28, 2020 varies from 2.3% in China, 2.7% in Iran, and 0.5% in South Korea. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79; 14.8% ≥80), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a reason for the higher mortality risk in these populations that is not apparent. We further present a set of pathophysiological reasons for the heightened danger could lead to therapies for enhanced management and prevention.

positive: Covid-19 and lung cancer: A greater fatality rate? BACKGROUND: Currently there are no reported series determining the Covid-19 infected lung cancer patient´s characteristics and outcome that allow us to clarify strategies to protect our patients. In our study we determine whether exists differences in cumulative incidence and severity of Covid-19 infection between lung cancer patients visiting our Medical Oncology department and the reference population of our center (320,000 people), in the current epicenter of the pandemic in Europe (Madrid, Spain). We also describe clinical and demographic factors associated with poor prognosis and Covid-19 treatment outcomes. PATIENTS AND METHODS: We retrospectively reviewed 1878 medical records of all Covid-19 patients who were admitted at Hospital Universitario Infanta Leonor of Madrid between March 5, 2020 and April 7, 2020, in order to detect cumulative incidence of Covid-19 in lung cancer patients. We also described Covid-19 treatment outcome, mortality and associated risk factors using univariate and multivariate logistic regression analysis. RESULTS: 17/1878 total diagnosis in our center had lung cancer (0.9%) versus 1878/320,000 of the total reference population (p = 0.09). 9/17 lung cancer patients with Covid-19 diagnosis died (52.3%) versus 192/1878 Covid-19 patients in our center (p<0.0001). Dead lung cancer patients were elderly compared to survivors: 72 versus 64.5 years old (p = 0.12). Combined treatment with hydroxychloroquine and azithromycin improves the outcome of Covid-19 in lung cancer patients, detecting only 1/6 deaths between patients under this treatment versus others treatment, with statistical significance in the univariate and multivariate logistic regression (OR 0.04, p = 0.018). CONCLUSIONS: Lung cancer patients have a higher mortality rate than general population. Combined hydroxychloroquine and azithromycin treatment seems like a good treatment option. It is important to try to minimize visits to hospitals (without removing their active treatments) in order to decrease nosocomial transmission.

positive: SARS‐CoV‐2, the Virus that Causes COVID‐19: Cytometry and the New Challenge for Global Health

positive: OpenSAFELY: factors associated with COVID-19 death in 17 million patients. COVID-19 has rapidly affected mortality worldwide1. There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England, here we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.30-1.69 and 1.44, 1.32-1.58, respectively). We have quantified a range of clinical risk factors for COVID-19-related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients' records; we will update and extend results regularly.

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

positive: Covid-19: Known risk factors fail to explain the increased risk of death among people from ethnic minorities.

positive: OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. Background Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Data sources Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. Population 17,425,445 adults. Time period 1st Feb 2020 to 25th April 2020. Primary outcome Death in hospital among people with confirmed COVID-19. Methods Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. Results There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10); older age and deprivation (both with a strong gradient); uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56); severe asthma (HR 1.25 CI 1.08-1.44); and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57; fully adjusted HR 1.71 95% CI 1.44-2.02); with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18; fully adjusted HR 1.62 95% CI 1.43-1.82). Conclusions We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation; further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients' records; we will update and extend these results regularly. Keywords COVID-19, risk factors, ethnicity, deprivation, death, informatics.

positive: Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients. OBJECTIVE. Available information on CT features of the 2019 novel coronavirus disease (COVID-19) is scattered in different publications, and a cohesive literature review has yet to be compiled. MATERIALS AND METHODS. This article includes a systematic literature search of PubMed, Embase (Elsevier), Google Scholar, and the World Health Organization database. RESULTS. Known features of COVID-19 on initial CT include bilateral multilobar ground-glass opacification (GGO) with a peripheral or posterior distribution, mainly in the lower lobes and less frequently within the right middle lobe. Atypical initial imaging presentation of consolidative opacities superimposed on GGO may be found in a smaller number of cases, mainly in the elderly population. Septal thickening, bronchiectasis, pleural thickening, and subpleural involvement are some of the less common findings, mainly in the later stages of the disease. Pleural effusion, pericardial effusion, lymphadenopathy, cavitation, CT halo sign, and pneumothorax are uncommon but may be seen with disease progression. Follow-up CT in the intermediate stage of disease shows an increase in the number and size of GGOs and progressive transformation of GGO into multifocal consolidative opacities, septal thickening, and development of a crazy paving pattern, with the greatest severity of CT findings visible around day 10 after the symptom onset. Acute respiratory distress syndrome is the most common indication for transferring patients with COVID-19 to the ICU and the major cause of death in this patient population. Imaging patterns corresponding to clinical improvement usually occur after week 2 of the disease and include gradual resolution of consolidative opacities and decrease in the number of lesions and involved lobes. CONCLUSION. This systematic review of current literature on COVID-19 provides insight into the initial and follow-up CT characteristics of the disease.

positive: The characteristics and death risk factors of 132 COVID-19 pneumonia patients with comorbidities: a retrospective single center analysis in Wuhan, China Background: The new coronavirus pneumonia (COVID-19) has evolved into a global pandemic disease, and the epidemiological characteristics of the disease have been reported in detail. However, many patients with new coronary pneumonia have comorbidities, and there are few researches reported in this special population. Methods: a retrospective analysis was performed on 132 consecutive COVID-19 patients with comorbidities from January 19, 2020 to March 7, 2020 in Hubei NO.3 People Hospital. Patients were divided into mild group and critical group and were followed up to the clinical endpoint. The observation biomarkers include the clinical feature, blood routine, blood biochemistry, inflammation biomarkers, and coagulation function. Univariate and multivariate logistic regression was used to analyze the risk factors associated with death. Results: 132 patients were enrolled in this study and divided into the mild group (n=109, 82.6%) and critical group (n=23, 17.4%), of whom 119 were discharged and 13 were died in hospital. The all-cause mortality rate was 9.8%, of which 7 patients died of respiratory failure, 5 patients died of heart failure, and 1 patient died of chronic renal failure. There was significant statistical difference of mortality rates between the mild group (5.5%) and the critical group (30.4%).The average time of hospitalization was 16.9 (9, 22) days. Hypertension was the most common comorbidity (n=90, 68.2%), followed by diabetes (n=45, 34.1%), coronary heart disease (31, 23.5%). Compared with the mild group, the patients were older in critical group (P <0.05), and neutrophils, neutrophil ratio, neutrophil-lymphocyte ratio (NLR), serum urea nitrogen (BUN), procalcitonin (PCT), C-reactive protein CRP), serum amyloid protein (SSA), N-terminal brain natriuretic peptide precursor (NT-pro BNP) were significantly increased (P <0.05). However, lymphocytes lymphocyte ratio, albumin were lower than those in the critical group (P <0.05). The patients were further divided into the survivor group (n=119, 90.2%) and the non-survivor group (n=13, 9.8%). Compared with the survivor group, the death rate of patients with coronary heart disease was significantly increased (53.8% vs 20.2%), and The neutrophil ratio, aspartate aminotransferase (AST), BUN, PCT, CRP, SAA, interleukin-6(IL-6) and D-dimer were significantly increased (P <0.05), while the lymphocytes and NLR reduced (P <0.05). Multivariate logistic stepwise regression analysis showed that the past medical history of coronary heart disease[OR:2.806 95%CI:0.971~16.795], decreased lymphocytes[OR:0.040, 95%CI:0.001~2.306], increased AST[OR:1.026, 95%CI:1.000~1.052], increased SSA[OR:1.021, 95%CI:1.001~1.025], and increased D-dimer[OR:1.231, 95%CI:1.042~1.456] are risk factors associated with death in COVID-19 patients pneumonia with comorbidities. Conclusion: The mortality rate of COVID-19 patients with coronary heart disease is relatively high. In all patients, the lower lymphocytes, and higher NLR, BUN, PCT, CRP, SSA, D-dimer are significant characteristics. The past medical history of coronary heart disease, decreased lymphocytes, increased AST, SSA and D-dimer are risk factors associated with death in COVID-19 pneumonia patients with comorbidities

positive: Emerging and reemerging respiratory viral infections up to Covid-19 Infectious diseases remain as the significant causes of human and animal morbidity and mortality, leading to extensive outbreaks and epidemics. Acute respiratory viral diseases claim over 4 million deaths and cause millions of hospitalizations in developing countries every year. Emerging viruses, especially the RNA viruses, are more pathogenic since most people have no herd immunity. The RNA viruses can adapt to the rapidly changing global and local environment due to the high error rate of their polymerases that replicate their genomes. Currently, coronavirus disease 2019 (COVID-19) is determined as an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in 2019 in Wuhan. Herein we discuss emerging and reemerging respiratory viral infections till to SARS-CoV-2.

positive: Registries Offer Insights on COVID-19-Cancer Connection. Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.

positive: Epidemiological analysis of the early 38 fatalities in Hubei, China, of the coronavirus disease 2019 BACKGROUND: Since the emergence of coronavirus disease 2019 (COVID-19) in Hubei province of China by the end of 2019, it has burned its way across the globe, resulting in a still fast-growing death toll that far exceeded those from severe acute respiratory syndrome (SARS) in less than two months. As there is a paucity of evidence on which population is more likely to progress into severe conditions among cases, we looked into the first cluster of death cases, aiming to add to current evidence and reduce panic among the population. METHODS: We prospectively collected the demographic and clinical data of the first 38 fatalities whose information was made public by the Health Commission of Hubei province and the official Weibo account of China Central Television news center, starting from 9 January through 24 January 2020. The death cases were described from four aspects (gender and age characteristics, underlying diseases, the time course of death, symptoms at the incipience of illness and hospital admission). RESULTS: Among the 38 fatalities, 71.05% were male, and 28.95% were female, with the median age of 70 years (interquartile range (IQR) = 65-81). Persons aged 66-75 made up the largest share. Twenty-five cases had a history of chronic diseases. The median time between the first symptoms and death was 12.50 days (IQR = 10.00-16.25), while the median time between the admission and death was 8.50 (IQR = 5.00-12.00) days. In persons aged over 56 years, the time between the first symptoms and death decreased with age, and so did the time between the admission and death, though the latter increased again in persons aged over 85 years. The major first symptoms included fever (52.63%), cough (31.58%), dyspnea (23.68%), myalgia and fatigue (15.79%). CONCLUSIONS: Among the death cases, persons with underlying diseases and aged over 65 made up the majority. The time between the first symptoms and death decreased with the advanced age. In all the age groups, males dominated the fatalities.

positive: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

positive: Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. Objective Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design Case series of 73 patients. Setting Large tertiary hospital in Milan. Participants Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures Demographic and daily clinical data were collected to identify predictors of early mortality. Results Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ; IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL; IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 μg/m; IQR, 5.0-23.8 μg/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12; 95% CI, 1.04-1.22; P = 0.004) and hypertension (OR, 6.15; 95% CI, 1.75-29.11; P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration ClinicalTrials.gov identifier: NCT04318366.

positive: Genetic risk factors for death with SARS-CoV-2 from the UK Biobank We present here genetic risk factors for survivability from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 19 (COVID-19). At the time of writing it is too early to determine comprehensively and without doubt all risk factors, but there is an urgency due to the global pandemic crisis that merits this early analysis. We have nonetheless discovered 5 novel risk variants in 4 genes, discovered by examining 193 deaths from 1,412 confirmed infections in a group of 5,871 UK Biobank participants tested for the virus. We also examine the distribution of these genetic variants across broad ethnic groups and compare it to data from the UK Office of National Statistics for increased risk of death from SARS-CoV-2. We confidently identify the gene ERAP2 with a high-risk variant, as well as three other genes of potential interest. Although mostly rare, a common theme of genetic risk factors affecting survival might be the inability to launch or modulate an effective immune and stress response to infection from the SARS-CoV-2 virus.

positive: Race/Ethnicity, Underlying Medical Conditions, Homelessness, and Hospitalization Status of Adult Patients with COVID-19 at an Urban Safety-Net Medical Center - Boston, Massachusetts, 2020. As of July 5, 2020, approximately 2.8 million coronavirus disease 2019 (COVID-19) cases and 130,000 COVID-19-associated deaths had been reported in the United States (1). Populations historically affected by health disparities, including certain racial and ethnic minority populations, have been disproportionally affected by and hospitalized with COVID-19 (2-4). Data also suggest a higher prevalence of infection with SARS-CoV-2, the virus that causes COVID-19, among persons experiencing homelessness (5). Safety-net hospitals,† such as Boston Medical Center (BMC), which provide health care to persons regardless of their insurance status or ability to pay, treat higher proportions of these populations and might experience challenges during the COVID-19 pandemic. This report describes the characteristics and clinical outcomes of adult patients with laboratory-confirmed COVID-19 treated at BMC during March 1-May 18, 2020. During this time, 2,729 patients with SARS-CoV-2 infection were treated at BMC and categorized into one of the following mutually exclusive clinical severity designations: exclusive outpatient management (1,543; 56.5%), non-intensive care unit (ICU) hospitalization (900; 33.0%), ICU hospitalization without invasive mechanical ventilation (69; 2.5%), ICU hospitalization with mechanical ventilation (119; 4.4%), and death (98; 3.6%). The cohort comprised 44.6% non-Hispanic black (black) patients and 30.1% Hispanic or Latino (Hispanic) patients. Persons experiencing homelessness accounted for 16.4% of patients. Most patients who died were aged ≥60 years (81.6%). Clinical severity differed by age, race/ethnicity, underlying medical conditions, and homelessness. A higher proportion of Hispanic patients were hospitalized (46.5%) than were black (39.5%) or non-Hispanic white (white) (34.4%) patients, a finding most pronounced among those aged <60 years. A higher proportion of non-ICU inpatients were experiencing homelessness (24.3%), compared with homeless patients who were admitted to the ICU without mechanical ventilation (15.9%), with mechanical ventilation (15.1%), or who died (15.3%). Patient characteristics associated with illness and clinical severity, such as age, race/ethnicity, homelessness, and underlying medical conditions can inform tailored strategies that might improve outcomes and mitigate strain on the health care system from COVID-19.

positive: Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. Results: Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions: In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5oC, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. Key words: 2019 novel coronavirus; acute respiratory infection; risk factors for disease severity

positive: The clinical characteristics and mortal causes analysis of COVID-19 death patients Abstract Purpose: Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients. Patients and methods: The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database. Results: 159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients. Conclusion: Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment . Keywords: COVID-19, SARS-Cov-2, death, coexisting disorder, cause of death

positive: 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.

positive: Dysfunctional Coagulation in COVID-19: From Cell to Bedside Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which can induce multisystem disease. Human angiotensin-converting enzyme 2 (ACE2) widely expressing in arterial and venous endothelial cells and arterial smooth muscle cells has been identified as a functional receptor for SARS-CoV-2. Dysfunction of ACE2 leads to abnormal activation of the renin-angiotensin system and a systemic endotheliitis that may relate to abnormal coagulation and sepsis. Meanwhile, innate immune response and inflammation activation participate in dysfunctional coagulation. Previous research indicated that dysfunctional coagulation was one of the important risk factors accountable for a high risk of severe disease and death in patients with COVID-19. Understanding the possible mechanisms of dysfunctional coagulation and appropriate anticoagulation therapeutic strategies are important to prevent disease deterioration and reduce fatality rates during the ongoing COVID-19 pandemic.

positive: The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis Background: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. Methods: We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Findings: Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB. Interpretation: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death. Funding Source: None

positive: Editorial: Coronaviruses: Facts, Myths and Hypotheses.

positive: Covid-19: Known risk factors fail to explain the increased risk of death among people from ethnic minorities

positive: Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: a retrospective cohort study BACKGROUND: In December, 2019, China, has experienced an outbreak of novel coronavirus disease 2019 (COVID-19). Coronavirus has now spread to all of the continents. We aimed to consider clinical characteristics, laboratory data of COVID-19 that provided more information for the research of this novel virus. METHODS: We performed a retrospective cohort study on the clinical symptoms and laboratory findings of a series of the 100 confirmed patients with COVID-19. These patients were admitted to the hospitals affiliated to Babol University of Medical Sciences (Ayatollah Rohani, Shahid Beheshti and Yahyanejad hospitals) form 25 February 2020 to 12 March 2020. RESULTS: Nineteen patients died during hospitalization and 81 were discharged. Non-survivor patients had a significantly higher C-reactive protein (CRP) (MD: 46.37, 95% CI: 20.84, 71.90; P= 0.001), white blood cells (WBCs) (MD: 3.10, 95% CI: 1.53, 4.67; P< 0.001) and lower lymphocyte (MD: -8.75, 95% CI: -12.62, -4.87; P< 0.001) compared to survivor patients Data analysis showed that comorbid conditions (aRR: 2.99, 95%CI: 1.09, 8.21, P= 0.034), higher CRP levels (aRR: 1.02, 95%CI: 1.01, 1.03, P= 0.044), and lower lymphocyte (aRR: 0.82, 95%CI: 0.73, 0.93, P= 0.003) were associated with increased risk of death. CONCLUSIONS: Based on our findings, most non-survivors are elderly with comorbidities. Lymphopenia and increased levels of WBCs along with elevated CRP were associated with increased risk of death. Therefore, it is best to be regularly assessed these markers during treatment of COVID-19 patients.

positive: Genes associated with liver damage signalling pathways may impact the severity of COVID-19 symptoms in Spanish and Italian populations Aim The novel SARS-CoV-2 virus, which causes the COVID-19 disease, has infected more than 10 million people and caused 500K deaths worldwide. In Europe, over 2 million confirmed cases have been reported, while nearly 200K people have died from the disease. Despite strict containment measures in Spain and Italy after the first reported COVID-19 patient, these two countries have remained in the top five European nations with the highest mortality rate for over two months. We hypothesised that a genetic mechanism could partially explain the poor survival outcome observed in these two countries. Methods An extensive literature search to identify human candidate genes linked to SARS-CoV infection, host immune evasion and disease aggressiveness was carried out. Pathway analysis (IPA) was performed to select the most significantly associated canonical signalling pathways with the genes of interest. The genetic variants’ at these genes with ±1Mb flanking region was extracted (GRCh37/hg19 built). Over 80 million single nucleotide polymorphisms (SNPs) were analysed in genome-wide data of 2,504 individuals (1000 genomes, phase III, https://www.internationalgenome.org/). Principal component (PC) analysis was performed, ancestry by the whole genome was inferred and subsets of the regions of interest were extracted (PLINK v1.9b, http://pngu.mgh.harvard.edu/purcell/plink/). PC1 to PC20 values from five European ancestries, including the Spanish and Italian populations, were used for PC analysis. Gene function predictions were run with our genes of interest as a query to the GeneMANIA Cytoscape plugin (https://genemania.org/). Results A total of 437 candidate genes associated with SARS were identified, including 21 correlated with COVID-19 aggressiveness. The two most significant pathways associated with all 437 genes (Caveolar-mediated Endocytosis and MSP-RON Signalling) did not show any segregation at the population level. However, the most significant canonical pathway associated with genes linked to COVID-19 aggressiveness, the Hepatic Fibrosis and Hepatic Stellate Cell Activation, showed population-specific segregation. Both the Spanish and Italian populations clustered together from the rest of Europe. This was also observed for the Finnish population but in the opposite direction. These results suggest some of the severe COVID-19 cases reported in Spain and Italy could be partially explained by a pre-existing liver condition (especially liver cancer) and/or may lead to further COVID-19 related liver complications.

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

positive: Guide to Understanding the 2019 Novel Coronavirus

positive: Dying with SARS-CoV-2 infection—an autopsy study of the first consecutive 80 cases in Hamburg, Germany Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1–3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

positive: Application of new topsis approach to identify the most significant risk factor and continuous monitoring of death of COVID-19 A pandemic is a disease that spreads across a large area like multiple continents or worldwide. More than 211 nations are already affected by Covid-19. The World Health Organization (WHO) on 11 March 2020 declared Covid19 a pandemic. There are more than 1,282,931 cases of the coronavirus illness over 211 countries and territories around the world. Currently coronavirus has no proper treatment in Medical Science, increasing the number of affected people day by day with the number of cases worldwide of novel coronavirus surpassing 1,282,931, with some 72,616 deaths approximately. That is why the main objective of the present investigation is to identify the significant risk factor. Also, in this study we are continuously monitoring the spread of coronavirus. In this study we use a new TOPSIS MCDM approach and GMDH apply to select the significant risk factor and continuous monitoring of death due to Covid-19. Result indicates that “contamination due to contact with the infected person” is the main responsible factor behind the pandemic COVID-19. Also, in this investigation we get an optimal model by which we can monitor the death from Coronavirus within the affected person continuously.

positive: 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.

positive: COVID-19 Fatality and Comorbidity Risk Factors among Confirmed Patients in Mexico As of April 18, 2020, 2.16 million patients in the world had been tested positive with Coronavirus (COVID-19) and 146,088 had died, which accounts for a case fatality rate of 6.76%. In Mexico, according to official statistics (April 18), 7,497 cases have been confirmed with 650 deaths, for a case fatality rate of 8.67%. These estimates, however, may not reflect the final fatality risk among COVID-19 confirmed patients, because they are based on cross-sectional counts of diagnosed and deceased patients, and therefore are not adjusted by time of exposure and right-censorship. In this paper we estimate fatality risks based on survival analysis methods, calculated from individual-level data on symptomatic patients confirmed with COVID-19 recently released by the Mexican Ministry of Health. The estimated fatality risk after 35 days of onset of symptoms is 12.38% (95% CI: 11.37-13.47). Fatality risks sharply rise with age, and significantly increase for males (59%) and individuals with comorbidities (38%-168%, depending on the disease). Two reasons may explain the high COVID-19 related fatality risk observed in Mexico, despite its younger age structure: the high selectivity and self-selectivity in testing and the high prevalence of chronic-degenerative diseases.

positive: Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ(2) test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56–70; range 14–96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59–78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56–6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16–10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57–9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.

positive: Laboratory findings and a combined multifactorial approach to predict death in critically ill patients with COVID-19: a retrospective study To describe the laboratory findings of cases of death with coronavirus disease 2019 (COVID-19) and to establish a scoring system for predicting death, we conducted this single-centre, retrospective, observational study including 336 adult patients (≥18 years old) with severe or critically ill COVID-19 admitted in two wards of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, who had definite outcomes (death or discharge) between 1 February 2020 and 13 March 2020. Single variable and multivariable logistic regression analyses were performed to identify mortality-related factors. We combined multiple factors to predict mortality, which was validated by receiver operating characteristic curves. As a result, in a total of 336 patients, 34 (10.1%) patients died during hospitalisation. Through multivariable logistic regression, we found that decreased lymphocyte ratio (Lymr, %) (odds ratio, OR 0.574, P < 0.001), elevated blood urea nitrogen (BUN) (OR 1.513, P = 0.009), and raised D-dimer (DD) (OR 1.334, P = 0.002) at admission were closely related to death. The combined prediction model was developed by these factors with a sensitivity of 100.0% and specificity of 97.2%. In conclusion, decreased Lymr, elevated BUN, and raised DD were found to be in association with death outcomes in critically ill patients with COVID-19. A scoring system was developed to predict the clinical outcome of these patients.

positive: ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China Background: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients. Methods: In this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports. Results: Of 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P <0.001), respectively. Conclusion: The ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas.

positive: Physician deaths from corona virus (COVID-19) disease BACKGROUND: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. AIMS: We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHODS: On 15 April 2020, a Google internet search was performed using the keywords ‘doctor’, ‘physician’, ‘death’, ‘COVID’ and ‘coronavirus’ in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. RESULTS: We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2% were infectious disease specialists (4/254), 6% were dentists (16/254), 4% were ENT (9/254) and 3% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44%), Iran (43/278; 15%), Philippines (21/278; 8%), Indonesia (17/278; 6%), China (16/278; 6%), Spain (12/278; 4%), USA (12/278; 4%) and UK (11/278;4%). CONCLUSIONS: Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.

positive: Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury. The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), p = 0.001; HR = 15.65 (95% CI = 2.43-100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p < 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

positive: COVID-19 and diabetes: Is there enough evidence? The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.

positive: Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System—a Call for Epidemiologic Investigations Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

positive: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus ≥65 years old; absolute risk of COVID-19 death in people <65 and in those ≥80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.

positive: No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: “COVID-19”, “nCov 19”, and “Sars Cov 2”. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: “death”, “died”, “comorbidity”, “cause of death”, “biopsy”, “autopsy”, or “pathological”. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.

positive: [Risks factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes]. OBJECTIVE The pathogenesis of myocardial injury upon corona virus disease 2019 (COVID-19) infection remain unknown,evidence of impact on outcome is insufficient, therefore, we aim to investigate the risk factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes in this study. METHODS This was a single-centered, retrospective, observational study. Patients of Sino-French Eco-City section of Tongji Hospital, Wuhan, China attended by Peking University Supporting Medical Team and admitted from Jan. 29, 2020 to Mar. 20, 2020 were included. The positive nucleic acid of COVID-19 virus and combination with hypertension, coronary heart disease or diabetes were in the standard. We collected the clinical data and laboratory examination results of the eligible patients to evaluate the related factors of death. RESULTS In the study, 94 COVID-19 patients enrolled were divided into the group of death (13 cases) and the group of survivors (81 cases), the average age was 66.7 years. Compared with the survival group, the death group had faster basal heart rate(103.2 beats/min vs. 88.4 beats /min, P=0.004), shortness of breath(29.0 beats /min vs. 20.0 beats /min, P<0.001), higher neutrophil count(9.2×109/L vs. 3.8×109/L, P<0.001), lower lymphocyte count(0.5×109/L vs. 1.1×109/L, P<0.001), creatine kinase MB(CK-MB, 3.2 μg/L vs. 0.8 μg/L, P<0.001), high sensitivity cardiac troponin Ⅰ(hs-cTnⅠ, 217.2 ng/L vs. 4.9 ng/L, P<0.001), N-terminal pro brain natriuretic peptide(NT-proBNP; 945.0 μg/L vs. 154.0 μg/L, P<0.001), inflammatory factor ferritin(770.2 μg/L vs. 622.8 μg/L , P=0.050), interleukin-2 recepter(IL-2R, 1 586.0 U/mL vs. 694.0 U/mL, P<0.001), interleukin-6(IL-6, 82.3 ng/L vs. 13.0 ng/L, P<0.001), interleukin-10(IL-10, 9.8 ng/L vs. 5.0 ng/L, P<0.001)were higher than those in the survival group. Univariate logistic regression analysis showed that the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, abnormal increase of IL 2R, IL-6, and IL-10. Multivariate regression showed that old age (OR=1.11, 95%CI=1.03-1.19, P=0.026), low non oxygen saturation(OR=0.85, 95%CI=0.72-0.99, P=0.041), and abnormal increase of IL-10(＞9.1 ng/L, OR=101.93, 95%CI=4.74-2190.71, P=0.003)were independent risk factors for COVID-19 patients combined with hypertension, coronary heart disease or diabetes. CONCLUSION In COVID-19 patients combined with hypertension, coronary heart disease or diabetes, the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, and abnormal increase of IL-2R, IL-6, and IL-10. Old age, low non oxygen saturation and abnormal increase of IL-10 were independent risk factors.

positive: Geographic Differences in COVID-19 Cases, Deaths, and Incidence - United States, February 12-April 7, 2020. Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States. Cumulative COVID-19 incidence varied substantially by jurisdiction, ranging from 20.6 cases per 100,000 in Minnesota to 915.3 in NYC. On April 7, national case doubling time was approximately 6.5 days, although this ranged from 5.5 to 8.0 days in the 10 jurisdictions reporting the most cases. Absolute change in cumulative incidence during March 31-April 7 also varied widely, ranging from an increase of 8.3 cases per 100,000 in Minnesota to 418.0 in NYC. Geographic differences in numbers of COVID-19 cases and deaths, cumulative incidence, and changes in incidence likely reflect a combination of jurisdiction-specific epidemiologic and population-level factors, including 1) the timing of COVID-19 introductions; 2) population density; 3) age distribution and prevalence of underlying medical conditions among COVID-19 patients (1-3); 4) the timing and extent of community mitigation measures; 5) diagnostic testing capacity; and 6) public health reporting practices. Monitoring jurisdiction-level numbers of COVID-19 cases, deaths, and changes in incidence is critical for understanding community risk and making decisions about community mitigation, including social distancing, and strategic health care resource allocation.

positive: 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.

positive: Long-Term Care Facilities as a Risk Factor for Death Due to COVID-19 A large percentage of the deaths from COVID-19 occur among residents of long-term care facilities. There are two possible reasons for this phenomenon. First, the structural features of such settings may lead to death. Alternatively, it is possible that individuals in these facilities are in poorer health than those living elsewhere, and that these individuals would have died even if they had not been in these facilities. Our findings show that, controlling for the population density and the percentage of older adults in the population, there is a significant positive association between the number of long-term care beds per capita and COVID-19 mortality rates. This finding provides support for the claim that long-term care living arrangements (of older people) are a significant risk factor for dying from COVID-19.

positive: COVID-19 autopsy in people who died in community settings: the first series. Here, we report the pathological findings of nine complete autopsies of individuals who died in community settings in the UK, three of which were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three tested negative for SARS-CoV-2 but are likely false negatives, and three died of other respiratory infections. Autopsy revealed firm, consolidated lungs or lobar pneumonia. Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space. This series is the first in the world to describe autopsy findings in individuals dying suddenly in the community, not previously known to have COVID-19 infection, and the first autopsy series in the UK. During a time when testing in the UK is currently primarily offered to patients in hospital or symptomatic key workers, with limited testing available in community settings, it highlights the importance of testing for COVID-19 at autopsy. Two deaths occurred in care homes where a diagnosis of COVID-19 allowed the health protection team to provide support in that 'closed setting' to reduce the risks of onward transmission. This work highlights the need for frequent COVID-19 testing in the management of patients in community settings. Comprehensive virology and microbiology assessment is pivotal to correctly identify the cause of death, including those due to COVID-19 infection, and to derive accurate death statistics.

positive: SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19?

positive: Race/Ethnicity, Underlying Medical Conditions, Homelessness, and Hospitalization Status of Adult Patients with COVID-19 at an Urban Safety-Net Medical Center - Boston, Massachusetts, 2020 As of July 5, 2020, approximately 2.8 million coronavirus disease 2019 (COVID-19) cases and 130,000 COVID-19-associated deaths had been reported in the United States (1). Populations historically affected by health disparities, including certain racial and ethnic minority populations, have been disproportionally affected by and hospitalized with COVID-19 (2-4). Data also suggest a higher prevalence of infection with SARS-CoV-2, the virus that causes COVID-19, among persons experiencing homelessness (5). Safety-net hospitals, such as Boston Medical Center (BMC), which provide health care to persons regardless of their insurance status or ability to pay, treat higher proportions of these populations and might experience challenges during the COVID-19 pandemic. This report describes the characteristics and clinical outcomes of adult patients with laboratory-confirmed COVID-19 treated at BMC during March 1-May 18, 2020. During this time, 2,729 patients with SARS-CoV-2 infection were treated at BMC and categorized into one of the following mutually exclusive clinical severity designations: exclusive outpatient management (1,543; 56.5%), non-intensive care unit (ICU) hospitalization (900; 33.0%), ICU hospitalization without invasive mechanical ventilation (69; 2.5%), ICU hospitalization with mechanical ventilation (119; 4.4%), and death (98; 3.6%). The cohort comprised 44.6% non-Hispanic black (black) patients and 30.1% Hispanic or Latino (Hispanic) patients. Persons experiencing homelessness accounted for 16.4% of patients. Most patients who died were aged ≥60 years (81.6%). Clinical severity differed by age, race/ethnicity, underlying medical conditions, and homelessness. A higher proportion of Hispanic patients were hospitalized (46.5%) than were black (39.5%) or non-Hispanic white (white) (34.4%) patients, a finding most pronounced among those aged <60 years. A higher proportion of non-ICU inpatients were experiencing homelessness (24.3%), compared with homeless patients who were admitted to the ICU without mechanical ventilation (15.9%), with mechanical ventilation (15.1%), or who died (15.3%). Patient characteristics associated with illness and clinical severity, such as age, race/ethnicity, homelessness, and underlying medical conditions can inform tailored strategies that might improve outcomes and mitigate strain on the health care system from COVID-19.

positive: Are African American and Hispanics Disproportionately Affected by COVID-19 Because of Higher Obesity Rates? INTRODUCTION: On March 13, 2020 the WHO declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in African American and Hispanics. The aim of this manuscript is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as it relates to the obesity rates to see whether this issue merits further evaluation. METHODS: COVID-19 data was obtained from the official New York (NY) authorities in relation to total number of cases in the different boroughs of NYC. Age adjusted COVID-19 related mortality rates of the different ethnic groups were also obtained. This data was cross compared to historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The two NYC boroughs that have the highest mortality rates are The Bronx (6%) and Brooklyn (5.4%). Both The Bronx and Brooklyn were also found to have the highest obesity rates 32% and 27% respectively. The two ethnic groups with the highest obesity rates (Hispanics and African Americans) were also found to have the highest age adjusted mortality rates per 100,000 compared to the other ethnic groups (22.8% and 19.8% respectively). CONCLUSION: Hispanics and African Americans in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.

positive: Toward understanding the 2019 Coronavirus and its impact on the heart

positive: Suppressed T cell-mediated immunity in patients with COVID-19: a clinical retrospective study in Wuhan, China Abstract Importance An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. Methods We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. Results A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge= 117) or non-survivors (in-hospital death=28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. Conclusion We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.

positive: COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy! The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community’s efforts, there is an increasing body of published studies describing the virus’ biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.

positive: Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications

positive: Why does COVID-19 disproportionately affect older people? The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient's age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients' ability to clear the infection and effectively regulate immune responses.

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: Covid-19: risk factors for severe disease and death

positive: Immunopathogenesis of coronavirus infections: implications for SARS At the end of 2002, the first cases of severe acute respiratory syndrome (SARS) were reported, and in the following year, SARS resulted in considerable mortality and morbidity worldwide. SARS is caused by a novel species of coronavirus (SARS-CoV) and is the most severe coronavirus-mediated human disease that has been described so far. On the basis of similarities with other coronavirus infections, SARS might, in part, be immune mediated. As discussed in this Review, studies of animals that are infected with other coronaviruses indicate that excessive and sometimes dysregulated responses by macrophages and other pro-inflammatory cells might be particularly important in the pathogenesis of disease that is caused by infection with these viruses. It is hoped that lessons from such studies will help us to understand more about the pathogenesis of SARS in humans and to prevent or control outbreaks of SARS in the future.

positive: Electrocardiographic Findings in COVID-19: Insights on Mortality and Underlying Myocardial Processes INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a respiratory syndrome with high rates of mortality, and there is a need for easily obtainable markers to provide prognostic information. We sought to determine whether the electrocardiogram (ECG) on hospital presentation provides prognostic information, specifically related to death. METHODS: We performed a retrospective cohort study in patients with COVID-19 who had an ECG at or near hospital admission. Clinical characteristics and ECG variables were manually abstracted from the electronic health record and first ECG. Our primary outcome was death. RESULTS: 756 patients who presented to a large New York City teaching hospital with COVID-19 underwent an ECG. The mean age was 63.3 ± 16 years, 37% were women, 61% of patients were non-white, and 57% had hypertension; 90 (11.9%) died. In a multivariable logistic regression that included age, ECG, and clinical characteristics, the presence of one or more atrial premature contractions (APC)s (odds ratio (OR)=2.57, 95% confidence interval (CI) 1.23-5.36, p=0.01), a right bundle branch block (RBBB) or intraventricular block (IVB) (OR=2.61, 95% CI 1.32-5.18, p=0.002), ischemic T-wave inversion (OR=3.49, 95% CI 1.56-7.80, p=0.002), and nonspecific repolarization (OR=2.31, 95% CI 1.27-4.21, p=0.006) increased the odds of death. ST elevation was rare (n=5, 0.7%). CONCLUSION: We found that patients with ECG findings of both left sided heart disease (APCs, IVB, repolarization abnormalities) and right sided disease (RBBB) have higher odds of death. ST elevation at presentation was rare.

positive: Association Between Hypoxemia and Mortality in Patients With COVID-19 Abstract Objective To identify markers associated with in-hospital death in patients with Coronavirus Disease 2019 (COVID-19) associated pneumonia. Patients and Methods Retrospective, cohort study of 140 patients with moderate-to-critical COVID-19 associated pneumonia requiring oxygen supplementation admitted from January 28th, 2020 to February 28th, 2020, and followed up through March, 13th 2020 in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis. Results Of 140 patients with COVID-19 associated pneumonia, 51.4% were men, with a median age of 60 years. Patients with SpO2 ≤90% were older, more likely to be men, to have hypertension and to present with dyspnea than those with SpO2 >90%. Overall, 36 (25.7%) patients died during hospitalization after a median 14-day follow-up. Higher post-oxygen supplementation SpO2 levels were associated with reduced mortality independently of age and sex (hazard ratio per 1-unit SpO2 0.93, 95% confidence interval, 0.91-0.95, P < .001). SpO2 cutoff of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio 2.60; 95% confidence interval 1.24-5.43, P = .01). Conclusions In this cohort of COVID-19 patients, hypoxemia was independently associated with in-hospital mortality. These results may help guide clinical management of severe COVID-19 patients, particularly in settings requiring strategic allocation of limited critical care resources.

positive: The natural history of symptomatic COVID-19 in Catalonia, Spain: a multi-state model including 109,367 outpatient diagnoses, 18,019 hospitalisations, and 5,585 COVID-19 deaths among 5,627,520 people Background The natural history of Coronavirus Disease 2019 (COVID-19) has yet to be fully described, with most previous reports focusing on hospitalised patients. Using linked patient-level data, we set out to describe the associations between age, gender, and comorbidities and the risk of outpatient COVID-19 diagnosis, hospitalisation, and/or related mortality. Methods A population-based cohort study including all individuals registered in Information System for Research in Primary Care (SIDIAP). SIDIAP includes primary care records covering > 80% of the population of Catalonia, Spain, and was linked to region-wide testing, hospital and mortality records. Outpatient diagnoses of COVID-19, hospitalisations with COVID-19, and deaths with COVID-19 were identified between 1st March and 6th May 2020. A multi-state model was used, with cause-specific Cox survival models estimated for each transition. Findings A total of 5,664,652 individuals were included. Of these, 109,367 had an outpatient diagnosis of COVID-19, 18,019 were hospitalised with COVID-19, and 5,585 died after either being diagnosed or hospitalised with COVID-19. Half of those who died were not admitted to hospital prior to their death. Risk of a diagnosis with COVID-19 peaked first in middle-age and then again for oldest ages, risk for hospitalisation after diagnosis peaked around 70 years old, with all other risks highest at oldest ages. Male gender was associated with an increased risk for all outcomes other than outpatient diagnosis. The comorbidities studied (autoimmune condition, chronic kidney disease, chronic obstructive pulmonary disease, dementia, heart disease, hyperlipidemia, hypertension, malignant neoplasm, obesity, and type 2 diabetes) were all associated with worse outcomes. Interpretation There is a continued need to protect those at high risk of poor outcomes, particularly the elderly, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death are lower for younger populations, there is a need to limit their role in community transmission. These findings should inform public health strategies, including future vaccination campaigns.

positive: Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population Background In December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population. Methods Retrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020. Results The study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n = 44), severe or critical patients (n = 25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; P < 0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Conclusions In this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.

positive: Risk Factors for Mortality in 244 Older Adults With COVID‐19 in Wuhan, China: A Retrospective Study BACKGROUND/OBJECTIVES: Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus‐2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID‐19) on admission, which may help identify those with poor prognosis at an early stage. DESIGN: Retrospective case‐control. SETTING: Fever ward of Sino‐French New City Branch of Tongji Hospital, Wuhan, China. PARTICIPANTS: Patients aged 60 years or older with COVID‐19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital. MEASUREMENTS: Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID‐19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death. RESULTS: Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001‐0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007‐1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in‐hospital death were similar between older men and women. CONCLUSION: Older age and lower LYM count on admission were associated with death in hospitalized COVID‐19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients.

positive: Higher mortality in men from COVID19 infection-understanding the factors that drive the differences between the biological sexes. The emergent global pandemic caused by the rapid spread of Severe Acute Respiratory syndrome- Coronavirus-2 (SARS-CoV-2) has led to increased mortality and negatively impacted day to day activities of humankind within a short period of time. As the data is rapidly emerging from earlier outbreak locations around the world, there are efforts to assimilate this with the knowledge from prior epidemics and find rapid solutions for this. One of the observations and a recurring theme is the disproportionate differences in the incidence of infection and the consequent mortality between males and females. We, therefore, analyzed retrospective datasets from the previous epidemics and the ongoing pandemic in order to address these differences in clinical outcomes. The data shows that even though the infection rates are similar, the odds ratio of male mortality remains high, indicating a divergence in the crosstalk between the three pathogenic human Coronavirus (hCoVs)- the SARS-CoV, MERS-CoV and the SARS-CoV-2 and immune effectors in the two sexes. One proximate cause is the sex-specific modulation of the X-linked genes that can influence susceptibility to infection. Future studies are needed to confirm these findings, which can form the basis for developing rational strategies for ending the current and preventing future pandemics.

positive: Characteristics and predictors of hospitalization and death in the first 9,519 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: A nationwide cohort Objective To provide population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) in order to inform targeted protection strategies in the general population and appropriate triage of hospital contacts. Design, Setting, and Participants Nationwide population-based cohort of all 228.677 consecutive Danish individuals tested (positive or negative) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from the identification of the first COVID-19 case on February 27th, 2020 until April 30th, 2020. Main Outcomes and Measures We examined characteristics and predictors of inpatient hospitalization versus community-management, and death versus survival, adjusted for age-, sex- and number of comorbidities. Results We identified 9,519 SARS-CoV-2 PCR-positive cases of whom 78% were community-managed, 22% were hospitalized (3.2% at an intensive care unit) and 5.5% had died within 30 days. Median age varied from 45 years (interquartile range (IQR) 31-57) among community-managed cases to 82 years (IQR 75-89) among those who died. Age was a strong predictor of fatal disease (odds ratio (OR) 14 for 70-79-year old, OR 26 for 80-89-year old, and OR 82 for cases older than 90 years, when compared to 50-59-year old and adjusted for sex and number of comorbidities). Similarly, the number of comorbidities was strongly associated with fatal disease (OR 5.2, for cases with [≥]4 comorbidities versus no comorbidities), and 82% of fatal cases had at least 2 comorbidities. A wide range of major chronic diseases were associated with hospitalization with ORs ranging from 1.3-1.4 (e.g. stroke, ischemic heart disease) to 2.2-2.7 (e.g. heart failure, hospital-diagnosed kidney disease, chronic liver disease). Similarly, chronic diseases were associated with mortality with ORs ranging from 1.2-1.3 (e.g. ischemic heart disease, hypertension) to 2.4-2.7 (e.g. major psychiatric disorder, organ transplantation). In the absence of comorbidities, mortality was relatively low (5% or less) in persons aged up to 80 years. Conclusions and Relevance In this first nationwide population-based study, increasing age and number of comorbidities were strongly associated with hospitalization requirement and death in COVID-19. In the absence of comorbidities, the mortality was, however, lowest until the age of 80 years. These results may help in accurate identification, triage and protection of high-risk groups in general populations, i.e. when reopening societies.

positive: Accelerated hyaluronan concentration as the primary driver of morbidity and mortality in high-risk COVID-19 patients: with therapeutic introduction of an oral hyaluronan inhibitor in the prevention of "Induced Hyaluronan Storm" Syndrome Background To date, more than 161,000 people have died from the coronavirus disease 2019 (COVID-19) yet the fundamental drivers of the morbidity and mortality remain uncertain. Clinicians worldwide appear to be at a loss to know how to prevent and treat the severe respiratory distress in these patients effectively. Consequently, the fundamental mechanisms leading to death in high-risk patients with COVID-19 need to be discovered and addressed with urgency. Despite a marked drop in frequency, the post-mortem autopsy remains an essential part of both discovering the cause of death in a particular individual, but also in advancing the science and treatment of disease, especially in the case of novel pathogens such as SARS-CoV-2[2]. The goal of an autopsy is to discover the cause of death (COD) using a macro/microscopic investigation. Traditionally, the intact organs are carefully removed, inspected, and weighed. Because lung weight is often affected by the cause of death and the last breath occurs very near if not at the moments of death, the evaluation of the lungs is one of the starting points of any COD investigation[3]. Method A comprehensive search was performed to systematically review all reported autopsy findings in COVID-19 patients in order to better understand the underlying disease mechanisms resulting in death. We then compared these findings with the results of a targeted literature review of hyaluronan in relationship to acute respiratory distress syndrome (ARDS). Results In total, data from 181 autopsies were identified. From this group, 6 autopsies of COVID-19 patients were selected for a detailed review and statistical analysis. The average lung weight of those who were determined to have died as a result of SARS-CoV-2 was 2196g-approximately 2.5x normal lung weight. Hyaline membranes were consistently identified on histologic sections. A review of the literature reveals that hyaluronan has been associated with the pathophysiology of ARDS since 1967. However, its key role in driving the morbidity and mortality of the condition has heretofore not been fully recognized. Conclusions We propose that the induced hyaluronan storm syndrome or IHS, is the model that best addresses the heretofore perplexing respiratory failure that is the proximal cause of death in a minority, but ever rising number, of patients. In addition to treating and preventing IHS in currently infected individuals now; an aggressive research effort should be undertaken to discover why the majority of individuals who are exposed to the virus are either minimally or asymptomatic, while a minority of high-risk individuals rapidly progress to respiratory failure and death. Keywords Systematic review; COVID-19; SARS-CoV-2; Hyaline Membrane; Hyaluronan; Acute Respiratory Distress Syndrome; ARDS; Autopsy; IHS; Induced Hyaluronan Storm Syndrome; COD; Cause of Death

positive: Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 AIMS: To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001]. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury. CONCLUSION: The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.

positive: 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.

positive: Predictors of Mortality for Patients with COVID-19 Pneumonia Caused by SARS-CoV-2: A Prospective Cohort Study To identify factors associated with the death for patients with COVID-19 pneumonia caused by a novel coronavirus SARS-CoV-2. All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital, Wuhan City, Hubei Province, China, between December 25, 2019 and February 7, 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk for death of COVID-19 pneumonia patients. A total of 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (odd ratio, 3.765; 95% confidence interval, 1.146‒17.394; p=0.023), preexisting concurrent cardiovascular or cerebrovascular diseases (2.464; 0.755‒8.044; p=0.007), CD3(+)CD8(+) T cells ≤75 cell·μL(−1) (3.982; 1.132‒14.006; p<0.001), and cardiac troponin I≥0.05 ng·mL(−1) (4.077; 1.166‒14.253; p<0.001) were associated with an increase in risk of mortality of COVID-19 pneumonia. In the sex‒, age‒, and comorbid illness-matched case study, CD3(+)CD8(+) T cells ≤75 cell·μL(−1) and cardiac troponin I≥0.05 ng·mL(−1) remained to be the predictors for high mortality of COVID-19 pneumonia. We identified four risk factors, age ≥65 years, preexisting concurrent cardiovascular or cerebrovascular diseases, CD3(+)CD8(+) T cells ≤75 cell·μL(−1), and cardiac troponin I≥0.05 ng·mL(−1), especially the latter two factors, were predictors for mortality of COVID-19 pneumonia patients.

positive: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)

positive: [Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy]. Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.

positive: The modified NUTRIC score can be used for nutritional risk assessment as well as prognosis prediction in critically ill COVID-19 patients BACKGROUND & AIMS: In the newly emerged Coronavirus Disease 2019 (COVID-19) disaster, little is known about the nutritional risks for critically ill patients. It is also unknown whether the modified Nutrition Risk in the Critically ill (mNUTRIC) score is applicable for nutritional risk assessment in intensive care unit (ICU) COVID-19 patients. We set out to investigate the applicability of the mNUTRIC score for assessing nutritional risks and predicting outcomes for these critically ill COVID-19 patients. METHODS: This retrospective observational study was conducted in three ICUs which had been specially established and equipped for COVID-19 in Wuhan, China. The study population was critically ill COVID-19 patients who had been admitted to these ICUs between January 28 and February 21, 2020. Exclusion criteria were as follows: 1) patients of ï¼18 years; 2) patients who were pregnant; 3) length of ICU stay of ï¼24 h; 4) insufficient medical information available. Patients' characteristics and clinical information were obtained from electronic medical and nursing records. The nutritional risk for each patient was assessed at their ICU admission using the mNUTRIC score. A score of ≥5 indicated high nutritional risk. Mortality was calculated according to patients' outcomes following 28 days of hospitalization in ICU. RESULTS: A total of 136 critically ill COVID-19 patients with a median age of 69 years (IQR: 57-77), 86 (63%) males and 50 (37%) females, were included in the study. Based on the mNUTRIC score at ICU admission, a high nutritional risk (≥5 points) was observed in 61% of the critically ill COVID-19 patients, while a low nutritional risk (<5 points) was observed in 39%. The mortality of ICU 28-day was significantly higher in the high nutritional risk group than in the low nutritional risk group (87% vs 49%, P ï¼0.001). Patients in the high nutritional risk group exhibited significantly higher incidences of acute respiratory distress syndrome, acute myocardial injury, secondary infection, shock and use of vasopressors. Additionally, use of a multivariate Cox analysis showed that patients with high nutritional risk had a higher probability of death at ICU 28-day than those with low nutritional risk (adjusted HR = 2.01, 95% CI: 1.22-3.32, P = 0.006). CONCLUSIONS: A large proportion of critically ill COVID-19 patients had a high nutritional risk, as revealed by their mNUTRIC score. Patients with high nutritional risk at ICU admission exhibited significantly higher mortality of ICU 28-day, as well as twice the probability of death at ICU 28-day than those with low nutritional risk. Therefore, the mNUTRIC score may be an appropriate tool for nutritional risk assessment and prognosis prediction for critically ill COVID-19 patients.

positive: COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies Summary The coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has reached pandemic status. As it spreads across the world, it has overwhelmed healthcare systems, strangled the global economy and led to a devastating loss of life. Widespread efforts from regulators, clinicians and scientists are driving a rapid expansion of knowledge of the SARS-CoV2 virus and the COVID-19 disease. We review the most current data with a focus on our basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. We discuss the basic virology, epidemiology, clinical manifestation, multi-organ consequences, and outcomes. With a focus on cardiovascular complications, we propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.

positive: Covid-19 and People with HIV Infection: Outcomes for Hospitalized Patients in New York City BACKGROUND: There have been limited data regarding the clinical impact of COVID-19 disease on people with HIV (PWH). In this study we compared outcomes for PWH with COVID-19 disease to a matched comparison group. DESIGN: We identified 88 PWH hospitalized with laboratory confirmed COVID-19 in our hospital system in New York between March 12 and April 23, 2020. We collected data on baseline clinical characteristics, laboratory values, HIV infection status, COVID-19 treatment, and outcomes from this group and matched comparators (one PWH to up to five patients by age, sex, race/ethnicity and calendar week of infection). We compared baseline clinical characteristics and outcomes (death, mechanical ventilation, hospital discharge) for these two groups, as well as cumulative incidence of death by HIV status. RESULTS: Patients did not differ significantly by HIV status by age, sex or race/ethnicity due to the matching algorithm. PWH hospitalized with COVID-19 had high proportions of HIV virologic control on antiretroviral therapy. PWH had greater proportions of smoking (p<0.001) and comorbid illness than demographically similar uninfected comparators. There was no difference in COVID-19 severity on admission by HIV status (p=0.15). Poor outcomes for hospitalized PWH were frequent but similar to proportions in comparators; 18% required mechanical ventilation and ultimately 21% died during follow-up (compared with 23% and 20% respectively). There was similar cumulative incidence of death over time by HIV status (p=0.94). INTERPRETATION: We found no differences in adverse outcomes associated with HIV infection for hospitalized COVID-19 patients compared to a demographically similar patient group.

positive: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study Background: Coronavirus disease-2019 (COVID-19) is a rapidly escalating epidemic caused by SARS-CoV-2. Identification of a simple and effective indicator to assess disease severity and outcome is urgently needed. Methods: This study retrospectively analyzed dynamic changes of lymphocyte percentage (LYM%) in 15 death cases, 15 severe cases as well as 40 moderate cases of COVID-19 patients. Next, prognostic role of lymphopenia in COVID-19 were verified in 92 hospitalized cases. Results: Our results from death and severe cases showed that LYM% in blood test were inversely associated with the progression and severity of COVID-19. LYM% in patients with moderate COVID-19 remained higher than 20% 10-12 days after symptom onset. In contrast, LYM% was lower than 20% in severe cases. However, LYM% in severe cases was higher than 5% 17-19 days after the onset of the disease, while it fell below 5% in death cases. Therefore, we established a reliable Time from symptom onset-LYM% model (TLM), which could be used to evaluate disease severity and predict the outcomes of hospitalized patients with COVID-19. Conclusion: Lymphopenia can be used to indicate clinical course, treatment effect and outcomes of COVID-19 patients.

positive: Prevalence and risk factors for mortality related to COVID-19 in a severely affected area of Madrid, Spain BACKGROUND: The coronavius disease 2019 (COVID-9) caused by the severe acute respiratory syndrome coronavirus 2 reached Spain by 31 January 2020, in April 2020, the Comunidad de Madrid suffered one of the world's highest crude mortality rate ratios. This study aimed to detect risk factors for mortality in patients with COVID-19. METHODS: Our cohort were all consecutive adult patients with laboratory-confirmed COVID-19 at a secondary hospital in Madrid, March 3-16, 2020. Clinical and laboratory data came from electronic clinical records and were compared between survivors and non-survivors, with outcomes followed up until April 4. Univariable and multivariable logistic regression methods allowed us to explore risk factors associated with in-hospital death. FINDINGS: The cohort comprised 562 patients with COVID-19. Clinical records were available for evaluation for 392 patients attended at the emergency department of our hospital, of whom 199 were discharged, 85 remained hospitalized and 108 died during hospitalization. Among 311 of the hospitalized patients, 34.7% died. Of the 392 patients with records, the median age was 71.5 years (50.6-80.7); 52.6% were men. 252 (64.3%) patients had a comorbidity, hypertension being the most common: 175 (44.6%), followed by other cardiovascular disease: 102 (26.0%) and diabetes: 97 (24.7%). Multivariable regression showed increasing odds of in-hospital death associated with age over 65 (odds ratio 8.32, 95% CI 3.01-22.96; p<0.001), coronary heart disease (2.76, 1.44-5.30; 0.002), and both lower lymphocyte count (0.34, 0.17-0.68; 0.002) and higher LDH (1.25, 1.05-1.50; 0.012) per 1-unit increase and per 100 units respectively. INTERPRETATION: COVID-19 was associated in our hospital at the peak of the pandemic with a crude mortality ratio of 19.2% and a mortality ratio of 34.7% in admitted patients, considerably above most of the ratios described in the Chinese series. These results leave open the question as to which factors, epidemiological or intrinsically viral, apart from age and comorbidities, can explain this difference in excess mortality. FUNDING: None.

positive: Clinical characteristics and prognostic factors in COVID‐19 patients aged ≥80 years AIM: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID‐19), and provide insights regarding the prognostic factors and the risk stratification in this population. METHODS: This was a single‐center, retrospective, observational study, carried out in a referral center for COVID‐19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID‐19 over a 1‐month period (1–31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni‐ and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden’s index. RESULTS: Overall, 69 patients, aged 80–98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82–89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID‐19 disease. A total of 23 (33.3%) patients had died at 30 days’ follow up. Multivariate Cox regression analysis showed that severe dementia, pO(2) ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. CONCLUSIONS: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID‐19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients. Geriatr Gerontol Int 2020; ••: ••–••.

positive: 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.

positive: 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.

positive: Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed

positive: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures: Confirmed COVID-19 pneumonia. Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

positive: 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).

positive: 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.

positive: 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.

positive: Risk Factors for Mortality in 244 Older Adults With COVID-19 in Wuhan, China: A Retrospective Study BACKGROUND/OBJECTIVES: Previous studies have reported that older patients may experience worse outcome(s) after infection with severe acute respiratory syndrome coronavirus-2 than younger individuals. This study aimed to identify potential risk factors for mortality in older patients with coronavirus disease 2019 (COVID-19) on admission, which may help identify those with poor prognosis at an early stage. DESIGN: Retrospective case-control. SETTING: Fever ward of Sino-French New City Branch of Tongji Hospital, Wuhan, China. PARTICIPANTS: Patients aged 60 years or older with COVID-19 (n = 244) were included, of whom 123 were discharged and 121 died in hospital. MEASUREMENTS: Data retrieved from electronic medical records regarding symptoms, signs, and laboratory findings on admission, and final outcomes of all older patients with COVID-19, were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to explore risk factors for death. RESULTS: Univariate analysis revealed that several clinical characteristics and laboratory variables were significantly different (ie, P < .05) between discharged and deceased patients. Multivariable logistic regression analysis revealed that lymphocyte (LYM) count (odds ratio [OR] = 0.009; 95% confidence interval [CI] = 0.001-0.138; P = .001) and older age (OR = 1.122; 95% CI = 1.007-1.249; P = .037) were independently associated with hospital mortality. White blood cell count was also an important risk factor (P = .052). The area under the receiver operating characteristic curve in the logistic regression model was 0.913. Risk factors for in-hospital death were similar between older men and women. CONCLUSION: Older age and lower LYM count on admission were associated with death in hospitalized COVID-19 patients. Stringent monitoring and early intervention are needed to reduce mortality in these patients. J Am Geriatr Soc 68:E19-E23, 2020.

positive: Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study Background. Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients. Methods. Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed. Results. Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities, including diabetes, hypertension, hepatic disease, cardiac disease, chronic pulmonary disease and others. Among all patients, critical cases, defined as oxygenation index lower than 200, accounted for 26.2%. Severe cases, oxygenation index from 200 to 300, were 29.7%. Besides, common cases, oxygenation index higher than 300, accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT and TBIL, two indexes of hepatic injury, AST, myoglobin and LDH, AST/ALT ratio, several markers of myocardial injury, creatinine, urea nitrogen and uric acid, three indexes of renal injury, were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients. Conclusion. Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators. Early hospitalization is of great significance to prevent multiple organ damage and improve the survival of COVID-19 patients.

positive: ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study The current SARS covid-19 epidemic spread appears to be influenced by ethnical, geographical and sex-related factors that may involve genetic susceptibility to diseases. Similar to SARS-CoV, SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells, notably type II alveolar epithelial cells. Importantly, ACE2 gene is highly polymorphic. Here we have used in silico tools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 spike glycoprotein. We found that S19P (common in African people) and K26R (common in European people) were, among the most diffused SNPs worldwide, the only two SNPs that were able to potentially affect the interaction of ACE2 with SARS-CoV-2 spike. FireDock simulations demonstrated that while S19P may decrease, K26R might increase the ACE2 affinity for SARS-CoV-2 Spike. This finding suggests that the S19P may genetically protect, and K26R may predispose to more severe SARS-CoV-2 disease.

positive: Risk factors for mortality of adult inpatients with Coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis of retrospective studies Background: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection. Methods: Online databases including Web of Science, PubMed, Scopus and Google scholar were searched to detect relevant publications up to 22 March 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done. Results: In total, six retrospective studies with 22,350 COVID-19 infected patients and 741 cases of death were included in the current meta-analysis. A significant positive association was found between older age (≥65 years old) and COVID-19 mortality (combined effect size=2.39 (over twofold), 95% CIs=1.75-3.28, p<0.001). Such finding was also seen for hypertension (combined effect size=3.29 (over threefold), 95% CIs=1.54-7.05, p=0.002), diabetes (combined effect size=3.11 (over threefold), 95% CIs=1.10-8.80, p=0.032), chronic obstructive pulmonary disease (COPD) (combined effect size=7.69 (over sevenfold), 95% CIs=5.65-10.47, p<0.001) and cardiovascular diseases (CVDs) (combined effect size=7.39 (over sevenfold), 95% CIs=2.88-18.96, p<0.001). Conclusions: Older age, hypertension, diabetes, COPD and CVDs were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.

positive: Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China IMPORTANCE: An ongoing outbreak of COVID-19 has exhibited significant threats around the world. We found a significant decrease of T lymphocyte subsets and an increase of inflammatory cytokines of hospitalized patients with COVID-19 in clinical practice. METHODS: We conducted a retrospective, single-center observational study of in-hospital adult patients with confirmed COVID-19 in Hubei Provincial Hospital of traditional Chinese and Western medicine (Wuhan, China) by Mar 1, 2020. Demographic, clinical, laboratory information, especially T lymphocyte subsets and inflammatory cytokines were reported. For patients who died or discharge from hospital, the associations of T lymphocyte subsets on admission were evaluated by univariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs), warning values to predict in-hospital death were assessed by Receiver Operator Characteristic (ROC) curves. RESULTS: A total of 187 patients were enrolled in our study from Dec 26, 2019 to Mar 1, 2020, of whom 145 were survivors (discharge = 117) or non-survivors (in-hospital death ==28). All patients exhibited a significant drop of T lymphocyte subsets counts with remarkably increasing concentrations of SAA, CRP, IL-6, and IL-10 compared to normal values. The median concentrations of SAA and CRP in critically-ill patients were nearly 4- and 10-fold than those of mild-ill patients, respectively. As the severity of COVID-19 getting worse, the counts of T lymphocyte drop lower.28 patients died in hospital, the median lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell and B-cell were significantly lower than other patients. Lower counts (/uL) of T lymphocyte subsets lymphocyte (<500), CD3+T-cell (<200), CD4+ T-cell (<100), CD8+ T-cell (<100) and B-cell (<50) were associated with higher risks of in-hospital death of CIVID-19. The warning values to predict in-hospital death of lymphocyte, CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and B-cell were 559, 235, 104, 85 and 82, respectively. CONCLUSION: We find a significant decrease of T lymphocyte subset is positively correlated with in-hospital death and severity of illness. The decreased levels of T lymphocyte subsets reported in our study were similar with SARS but not common among other virus infection, which may be possible biomarkers for early diagnosis of COVID-19. Our findings may shed light on early warning of high risks of mortality and help early intervention and treatment of COVID-19.

positive: Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. OBJECTIVE: We sought to evaluate the severity on admission, complications, treatment, and outcomes of patients with COVID-19. 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. Older age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-α), and high lactate dehydrogenase level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in patients with COVID-19 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 sex, older age, leukocytosis, high lactate dehydrogenase level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. CONCLUSIONS: Patients with older age, hypertension, and high lactate dehydrogenase 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 a high risk of death.

positive: Pathologists in pursuit of the COVID-19 culprit

positive: Are patients with Down syndrome vulnerable to life-threatening COVID-19? Patients with Down syndrome are at increased risk of respiratory syncytial virus- and H1N1-related death. Literature on COVID-19 in Down syndrome patients is unavailable thus far. We describe the clinical course of 4 patients with Down syndrome during an outbreak of COVID-19. In all four patients, disease course was severe, warranting hospital care in three patients, with fatal outcome in one patient. Another patient receives supportive care in our institution. Our case series is the first report on probable increased risk of life-threatening disease course of COVID-19 in patients with Down syndrome. Proper surveillance, the adherence of social distancing, and the use of personal protective equipment will be essential in reducing morbidity and mortality in our patients.

positive: 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.

positive: [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.

positive: Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19 Abstract Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any ”normal” post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart. Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.

positive: An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.

positive: The characteristics and outcomes of 681 severe cases with COVID-19 in China PURPOSE: To clarify the epidemiological, clinical, and therapeutic features of patients with severe COVID-19. METHODS: In this study, we enrolled 681 patients with confirmed cases of severe COVID-19. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected. RESULTS: The median age of the study participants was 65 years, 53.2% were male, and 104 (15.3%) died. Age, Neutrophil-To-Lymphocyte Ratio (NLR), acute myocardial injury, and levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD3 T cells counts were independently and negatively associated with death, while arbidol and ribavirin were protective from death. The combination of NLR and acute myocardial injury on admission (AUC = 0.914) predicted mortality better than NLR, CRP, LDH, and acute myocardial injury. There were 312 (45.8%) patients with cardiovascular disease, of whom 23.4% died. β-blockers, ACEI/ARB, arbidol, and ribavirin might have a beneficial effect for severe COVID-19 patients with cardiovascular disease. CONCLUSION: The combination of NLR and acute myocardial injury on admission was highly predictive of mortality and survival. Clinicians should adopt more aggressive strategies for patients with a high NLR (>6.66) combined with myocardial injury. β-blockers and ACEI/ARB, as well as arbidol and ribavirin, were effective in COVID-19 patients with cardiovascular disease.

positive: 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

positive: Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS AND RESULTS: This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS: This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.

positive: A Review of Acute Myocardial Injury in Coronavirus Disease 2019 In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, Hubei province, China, and it has spread rapidly across the world, causing the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 infection predominantly results in pulmonary issues, accumulating evidence suggests the increased frequency of a variety of cardiovascular complications in patients with COVID-19. Acute cardiac injury, defined as elevated cardiac troponin levels, is the most reported cardiac abnormality in COVID-19 and strongly associated with mortality. In this article, we summarize the currently available data on the association of SARS-CoV-2 and COVID-19 with acute myocardial injury.

positive: Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243).

positive: Coronavirus disease 2019 (COVID-19): current status and future perspectives ABSTRACT Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics.

positive: Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. Purpose: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection.Methods: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done.Results: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (≥65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality.Conclusions: Older age (≥65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.

positive: 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.

positive: Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47–69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63–73) vs 55 (IQR 35–60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7–13) vs 12 (IQR 11–43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.

positive: AKI during COVID-19 infection: low incidence, high risk of death Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide and seriously threatens human health since December 2019. However, information about acute kidney injury (AKI) during COVID-19 infection is limited. Some studies thought that presence of AKI is very common and cannot be ignored, while some studies pointed that AKI only is a rare incident during COVID-19 infection. This meta-analysis aimed to find out the truth of COVID-19 related AKI and to provide stronger evidence. Methods: Two authors independently performed a literature search using PubMed, Web of Science, Embase, and Cochrane Library fulfilled the pre-specified criteria until April 25, 2020 to include studies reported the necessary clinic characteristics, then the incidence of AKI, incidence of required RRT, the mortality with AKI and the death risk with AKI during COVID-19 infection were pooled for statistical analysis by Open Meta-Analyst software to get conclusions. Findings: It was found that the incidence of AKI in hospitalized patients with COVID-19 infection is low, only about 3.8%; the in-hospital mortality with AKI in COVID-19 infected patients is reach up to 32.6%; the death risk with AKI in COVID-19 infected patients is about 16.1 times higher than those without AKI. Conclusions: This meta-analysis indicated AKI during COVID-19 infection should be pay more attention, it maybe a strong red flag to death risk. It is still need additional studies to support the conclusions and to explore the AKI mechanism during COVID-19 infection.

positive: 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

positive: Inhibitors of the Renin–Angiotensin–Aldosterone System and Covid-19

positive: Impact of diabetes mellitus on clinical outcomes in patients affected by Covid-19 A possible association could exist between type 2 diabetes mellitus (T2DM) and Coronavirus-19 (Covid-19) infection. Indeed, patients with T2DM show high prevalence, severity of disease and mortality during Covid-19 infection. However, the rates of severe disease are significantly higher in patients with diabetes compared with non-diabetes (34.6% vs. 14.2%; p < 0.001). Similarly, T2DM patients have higher rates of need for Intensive Care Unit (ICU, 37.0% vs. 26.7%; p = 0.028). Thus, about the pneumonia of Covid-19, we might speculate that the complicated alveolar-capillary network of lungs could be targeted by T2DM micro-vascular damage. Therefore, T2DM patients frequently report respiratory symptoms and are at increased risk of several pulmonary diseases. In addition, pro-inflammatory pathways as that involving interleukin 6 (IL-6), could be a severity predictor of lung diseases. Therefore, it looks intuitive to speculate that this condition could explain the growing trend of cases, hospitalization and mortality for patients with T2DM during Covid-19 infection. To date, an ongoing experimental therapy with monoclonal antibody against the IL-6 receptor in Italy seems to have beneficial effects on severe lung disease and prognosis in patients with Covid-19 infection. Therefore, should patients with T2DM be treated with more attention to glycemic control and monoclonal antibody against the IL-6 receptor during the Covid-19 infection?

positive: From causes of aging to death from COVID-19 COVID-19 is not deadly early in life, but mortality increases exponentially with age, which is the strongest predictor of mortality. Mortality is higher in men than in women, because men age faster, and it is especially high in patients with age-related diseases, such as diabetes and hypertension, because these diseases are manifestations of aging and a measure of biological age. At its deepest level, aging (a program-like continuation of developmental growth) is driven by inappropriately high cellular functioning. The hyperfunction theory of quasi-programmed aging explains why COVID-19 vulnerability (lethality) is an age-dependent syndrome, linking it to other age-related diseases. It also explains inflammaging and immunosenescence, hyperinflammation, hyperthrombosis, and cytokine storms, all of which are associated with COVID-19 vulnerability. Anti-aging interventions, such as rapamycin, may slow aging and age-related diseases, potentially decreasing COVID-19 vulnerability.

positive: Clinical characteristics of 82 cases of death from COVID-19 A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. 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. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (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%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On 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%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms 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 symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.

positive: 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 two novel coronavirus outbreaks in the past two decades. The 2002-2003 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 death), 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.

positive: Covid-19: risk factors for severe disease and death.

positive: Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study This study described the epidemiologic and clinical characteristics of patients who died from SARS-CoV-2 infection, and pointed out the potential risk factors associated with fatal outcomes. Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, China was analyzed. Demographics, clinical detection, laboratory findings, and treatments of the deceased were collected and analyzed. The average time between onset of symptoms and admission to the hospitals was 11 ± 5 days of hospitalization. Among the deceased, 60% were with co-morbidities. All of them were having fever and bilateral pneumonia on computed tomography, abnormal infection-related biomarkers, and renal impairment. Abnormal blood coagulation parameters that appeared in more than half of them, were consistent with disseminated intravascular coagulation. All of the patients were treated in the ICU. Based on the fact that SARS-CoV-2 infection carries a risk of mortality, we may infer a few older male patients with underlying comorbidities are likely to have the increased risk. Impaired consciousness level, markers of renal impairment and coagulation abnormalities may be poor prognostic factors.

positive: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

positive: Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis INTRODUCTION: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. METHODS: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). RESULTS: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5–92.9%), cough (57.6%, 95%CI 40.8–74.4%) and dyspnea (45.6%, 95%CI 10.9–80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0–30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7–51.8), 6.2% (95%CI 3.1–9.3) with shock. Some 13.9% (95%CI 6.2–21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). CONCLUSION: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.

positive: Can We Reduce Mortality of COVID-19 if We do Better in Glucose Control? The SARS-CoV-2 has infected more than 3 million people and caused more than 240,000 death globally. Among the COVID-19 patients, the prevalence of people with other chronic diseases, such as diabetes, high blood pressure, and coronary heart disease is much higher than others. More strikingly, the survival rate of diabetic patients is also much lower than in non-diabetic patients. In addition to the general damage of high glucose to cells and tissues, a recent discovery that high glucose activates interferon regulatory factor 15 promotes influenza virus -induced cytokine storm. This discovery may shed light on the high incidence of diabetes in COVID-19. Several diabetes prevention strategies together with recent significant data-driven diabetes prediction approaches, which may help COVID-19 treatments, have been proposed.

positive: Ethnicity and outcomes in patients hospitalised with COVID-19 infection in East London: an observational cohort study Background: Preliminary studies suggest that people from Black, Asian and Minority Ethnic (BAME) backgrounds experience higher mortality from COVID-19 but the underlying reasons remain unclear. Methods: Prospective analysis of registry data describing patients admitted to five acute NHS Hospitals in east London, UK for COVID-19. Emergency hospital admissions with confirmed SARS-CoV-2 aged 16 years or over were included. Data, including ethnicity, social deprivation, frailty, patient care and detailed risk factors for mortality, were extracted from hospital electronic records. Multivariable survival analysis was used to assess associations between ethnic group and mortality accounting for the effects of age, sex and various other risk factors. Results are presented as hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals. Findings: 1996 adult patients were admitted between 1st March and 13th May 2020. After excluding 259 patients with missing ethnicity data, 1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) Black and 707 (40%) white backgrounds. Compared to white patients, those from BAME backgrounds were younger, with differing co-morbidity profiles and less frailty. Asian and black patients were more likely to be admitted to intensive care and to receive invasive ventilation (OR 1.54, [1.06-2.23]; p=0.023 and 1.80 [1.20-2.71]; p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49 [1.19-1.86]; p<0.001) and black (HR 1.30 [1.02-1.65]; p=0.036) backgrounds were more likely to die. These findings persisted across a range of risk-factor adjusted analyses. Interpretation: Patients from Asian and Black backgrounds are more likely to die from COVID-19 infection despite controlling for all previously identified confounders. Higher rates of invasive ventilation in intensive care indicate greater acute disease severity. Our analyses suggest that patients of Asian and Black backgrounds suffered disproportionate rates of premature death from COVID-19.

positive: ACE2 variants underlie interindividual variability and susceptibility to COVID-19 in Italian population In December 2019, an initial cluster of unexpected interstitial bilateral pneumonia emerged in Wuhan, Hubei province. A human-to-human transmission was immediately assumed and a previously unrecognized entity, termed coronavirus disease 19 (COVID-19) due to a novel coronavirus (2019-nCov) was suddenly described. The infection has rapidly spread out all over the world and Italy has been the first European Country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has recently been shown that 2019-nCov utilizes host receptors namely angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined around 7000 exomes from 5 different Centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three missense changes, p.Asn720Asp, p.Lys26Arg, p.Gly211Arg (MAF 0.002 to 0.015), which have never been reported in the Eastern Asia population, were predicted to interfere with protein cleavage and stabilization. Rare truncating variants likely interfering with the internalization process and one missense variant, p.Trp69Cys, predicted to interfere with 2019-nCov spike protein binding were also observed. These findings suggest that a predisposing genetic background may contribute to the observed inter-individual clinical variability associated with COVID-19. They allow an evidence-based risk assessment opening up the way to personalized preventive measures and therapeutic options.

positive: Laboratory abnormalities and risk factors associated with in-hospital death in patients with severe COVID-19. BACKGROUND In the context of the COVID-19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in-hospital death in patients with severe COVID-19. METHODS All ≥18-year-old patients with confirmed severe COVID-19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in-hospital death. RESULTS A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow-up period. The median age of non-survivors was significantly older than survivors (69 [64-76.5] years vs 64 [56-71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non-survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 × 109 /L (OR, 58.35; 95%CI: 2.16-1571.69; P = .016), hypersensitivity C-reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29-171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45-4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36-91.62; P = .024) were risk factors for in-hospital death. CONCLUSION The risk factors of neutrophil count, hypersensitivity C-reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID-19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID-19.

positive: 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.

positive: Assessing Differential Impacts of COVID-19 on Black Communities PURPOSE: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. METHODS: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. RESULTS: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. CONCLUSIONS: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.

positive: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract Abstract MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.

positive: Interim Analysis of Risk Factors for Severe Outcomes among a Cohort of Hospitalized Adults Identified through the U.S. Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET) Background: As of May 15, 2020, the United States has reported the greatest number of coronavirus disease 2019 (COVID-19) cases and deaths globally. Objective: To describe risk factors for severe outcomes among adults hospitalized with COVID-19. Design: Cohort study of patients identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network. Setting: 154 acute care hospitals in 74 counties in 13 states. Patients: 2491 patients hospitalized with laboratory-confirmed COVID-19 during March 1-May 2, 2020. Measurements: Age, sex, race/ethnicity, and underlying medical conditions. Results: Ninety-two percent of patients had at least 1 underlying condition; 32% required intensive care unit (ICU) admission; 19% invasive mechanical ventilation; 15% vasopressors; and 17% died during hospitalization. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84 and 85+ years versus 18-39 years (adjusted risk ratio (aRR) 1.53, 1.65, 1.84 and 1.43, respectively); male sex (aRR 1.34); obesity (aRR 1.31); immunosuppression (aRR 1.29); and diabetes (aRR 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84 and 85+ years versus 18-39 years (aRR 3.11, 5.77, 7.67 and 10.98, respectively); male sex (aRR 1.30); immunosuppression (aRR 1.39); renal disease (aRR 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR 1.28); neurologic disorders (aRR 1.25); and diabetes (aRR 1.19). Race/ethnicity was not associated with either ICU admission or death. Limitation: Data were limited to patients who were discharged or died in-hospital and had complete chart abstractions; patients who were still hospitalized or did not have accessible medical records were excluded. Conclusion: In-hospital mortality for COVID-19 increased markedly with increasing age. These data help to characterize persons at highest risk for severe COVID-19-associated outcomes and define target groups for prevention and treatment strategies.

positive: Risk factors affecting COVID-19 case fatality rate: A quantitative analysis of top 50 affected countries Background: Latest clinical data on treatment on coronavirus disease 2019 (COVID-19) indicated that older patients and those with underlying history of smoking, hypertension or diabetes mellitus might have poorer prognosis of recovery from COVID-19. We aimed to examine the relationship of various prevailing population-based risk factors in comparison with mortality rate and case fatality rate (CFR) of COVID-19. Methods: Demography and epidemiology data which have been identified as verified or postulated risk factors for mortality of adult inpatients with COVID-19 were used. The number of confirmed cases and the number of deaths until April 16, 2020 for all affected countries were extracted from Johns Hopkins University COVID-19 websites. Datasets for indicators that are fitting with the factors of COVID-19 mortality were extracted from the World Bank database. Out of about 185 affected countries, only top 50 countries were selected to be analyzed in this study. The following seven variables were included in the analysis, based on data availability and completeness: 1) proportion of people aged 65 above, 2) proportion of male in the population, 3) diabetes prevalence, 4) smoking prevalence, 5) current health expenditure, 6) number of hospital beds and 7) number of nurses and midwives. Quantitative analysis was carried out to determine the correlation between CFR and the aforementioned risk factors. Results: United States shows about 0.20% of confirmed cases in its country and it has about 4.85% of CFR. Luxembourg shows the highest percentage of confirmed cases of 0.55% but a low 2.05% of CFR, showing that a high percentage of confirmed cases does not necessarily lead to high CFR. There is a significant correlation between CFR, people aged 65 and above (p = 0.35) and diabetes prevalence (p = 0.01). However, in our study, there is no significant correlation between CFR of COVID-19, male gender (p = 0.26) and smoking prevalence (p = 0.60). Conclusion: Older people above 65 years old and diabetic patients are significant risk factors for COVID-19. Nevertheless, gender differences and smoking prevalence failed to prove a significant relationship with COVID-19 mortality rate and CFR. Keywords: Coronavirus, COVID-19, risk, epidemiology, fatality, age, diabetes

positive: 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.

positive: 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study Background: Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. Methods: This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Results: Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Conclusions: Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.

positive: Clinical Characteristics and Outcomes of 74 Patients With Severe or Critical COVID-19. BACKGROUND The outbreak of the coronavirus disease (COVID-19) has led to a major concern and caused a pandemic globally. The goal of this study was to clarify the clinical characteristics of recovery and death in patients with severe or critical COVID-19. MATERIALS AND METHODS In this retrospective single-center study, clinical data were collected from 74 severe or critical COVID-19 patients in Wuhan Fourth Hospital between Jan. 25th and Feb. 26th, 2020. All patients were divided into a recovery group or a death group according to clinical outcomes, and the differences between the groups were compared. RESULTS Of the 74 patients enrolled in the study, 48 (64.9%) were severe cases and 26 (35.1%) were critical cases. Sixty (81.1%) patients were recovered and 14 (18.9%) died. Compared with recovery patients, patients in the death group were older, and had higher incidences of hypertension, coronary disease and dyspnea at admission. Laboratory tests for lactate dehydrogenase, creatine kinase, myoglobin, brain natriuretic peptide and D-dimer indicated higher levels in the death group. The PaO2:FiO2 ratio and minimum SpO2 were lower in the death group, and a higher proportion of these patients received noninvasive mechanical ventilation, invasive mechanical ventilation and extracorporeal membrane oxygenation treatment. CONCLUSIONS Elderly patients with comorbidities are at higher risk of severe COVID-19 or death. Patients with a low blood gas index and poor coagulation function at admission had a high mortality rate. For such patients, comprehensive treatment should be performed as soon as possible to improve the prognosis and reduce mortality.

positive: 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.

positive: Analysis on 54 Mortality Cases of Coronavirus Disease 2019 in the Republic of Korea from January 19 to March 10, 2020 Since the identification of the first case of coronavirus disease 2019 (COVID-19), the global number of confirmed cases as of March 15, 2020, is 156,400, with total death in 5,833 (3.7%) worldwide. Here, we summarize the morality data from February 19 when the first mortality occurred to 0 am, March 10, 2020, in Korea with comparison to other countries. The overall case fatality rate of COVID-19 in Korea was 0.7% as of 0 am, March 10, 2020.

positive: Potential Impact of SARS-CoV-2 Infection in HIV-positive Patients in South Africa Coronaviruses are important causes of infection in both humans and animals. While in the past they were considered to be relatively harmless respiratory pathogens, outbreaks of infection with severe acute respiratory syndrome (SARS), Middle East respiratory syndrome, and currently SARS-CoV-2, have confirmed how serious these pathogens can be in respiratory tract infections. Certain conditions and underlying comorbidities are known to be risk factors for SARS-CoV-2 infection, and for associated severe disease, including older age, underlying chronic cardiovascular and respiratory conditions and diabetes mellitus. There are a number of additional conditions and comorbidities that are suspected as being important risk factors, but for which hard evidence is currently lacking. This includes underlying human immunodeficiency virus infection, which represents the major focus of this current survey of the scientific literature.

positive: Understanding pathways to death in patients with COVID-19

positive: Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft)(‡) Autopsy is of great significance for elucidating the pathological changes, pathogenesis and cause of death of Coronavirus Disease 2019 (COVID-19) and can provide a theoretical basis for scientific and accurate prevention and control of its outbreak. Based on related laws and regulations, such as the Law of the People’s Republic of China on Prevention and Control of Infectious Diseases, clinical manifestations and epidemiological characteristics of COVID-19 and guidelines on the prevention and control of this epidemic, combined with the practical work of forensic pathology examinations, we developed the Guide to Forensic Pathology Practice for Death Cases Related to Coronavirus Disease 2019 (COVID-19) (Trial Draft). This guide describes the background investigation of the death cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy practices and auxiliary examinations, and thus offers a reference for forensic and pathological examination institutions and staff.

positive: Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a serious of clinical symptoms and severe illness, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining were performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of Alveolar macrophage by SARS-CoV-2 might be drivers of the “cytokine storm”, which might result in damages in pulmonary tissues, heart and lung, and leading to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China

positive: COVID-19 pandemic, coronaviruses, and diabetes mellitus The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.

positive: Clinical characteristics of 82 cases of death from COVID-19. A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. 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. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (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%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On 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%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms 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 symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.

positive: Global epidemiology of coronavirus disease 2019 (COVID-19): disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status ABSTRACT It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.

positive: Prevalence of comorbidities in patients and mortality cases affected by SARS-CoV2: a systematic review and meta-analysis The new coronavirus, COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020. Risk factors associated with this disease are age, sex, and the presence of comorbidities, the most common being hypertension, diabetes, and heart disease. The aim of this meta-analysis was to calculate the prevalence and geographical distribution of comorbidities in all patients admitted to intensive care units (ICUs), and the mortality rate of COVID-19. We selected studies based upon epidemiological and clinical descriptions of the patients and mortality from the disease to determine the pooled prevalence of comorbidities in all patients and in mortality cases due to COVID-19. The pooled prevalence was estimated using the random effects model, and odds ratios were used to measure the probability of death for a patient with a comorbidity. The total prevalence of comorbidities in patients with COVID-19 was 42% (95% CI: 25-60), 61% (95% CI: 42-80) in those admitted to the ICU, and 77% (95% CI: 68-86) among death cases; males were the most affected. Hypertension was the most prevalent comorbidity in all three groups studied, accounting for 32%, 26%, and 35%, respectively. The odds ratio of death for a patient with a comorbidity compared to one with no comorbidity was 2.4 (P < 0.0001). The higher the prevalence of comorbidities the higher the odds that the COVID-19 patient will need intensive care or will die, especially if the pre-existing disease is hypertension, heart disease, or diabetes.

positive: Physician Deaths from Corona Virus Disease (COVID-19) OBJECTIVE: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHOD: On April 5, 2020, Google internet search was performed using the keywords doctor, physician, death, COVID, COVID-19, and coronavirus in English and Farsi, and in Chinese using the Baidu search engine. RESULTS: We found 198 physician deaths from COVID-19, but complete details were missing for 49 individuals. The average age of the physicians that died was 63.4 years (range 28 to 90 years) and the median age was 66 years of age. Ninety percent of the deceased physicians were male (175/194). General practitioners and emergency room doctors (78/192), respirologists (5/192), internal medicine specialists (11/192) and anesthesiologists (6/192) comprised 52% of those dying. Two percent of the deceased were epidemiologists (4/192), 2% were infectious disease specialists (4/192), 5% were dentists (9/192), 4% were ENT (8/192), and 4% were ophthalmologists (7/192). The countries with the most reported physician deaths were Italy (79/198), Iran (43/198), China (16/198), Philippines (14/198), United States (9/192) and Indonesia (7/192). CONCLUSION: Physicians from all specialties may die from COVID, and these deaths will likely increase as the pandemic progresses. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.

positive: Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%.Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia.Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020.Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively.Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

positive: Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 AIMS: To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87–0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001]. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28–16.28; P = 0.019) and 1.25 (95% CI, 1.07–1.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury. CONCLUSION: The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.

positive: 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.

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: 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.

positive: A geroscience perspective on COVID-19 mortality A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.

positive: The Outbreak of COVID-19 in Italy: Fighting the Pandemic

positive: D‐dimer levels on admission to predict in‐hospital mortality in patients with Covid‐19 BACKGROUND: The outbreak of the coronavirus disease 2019 (Covid‐19) shows a global spreading trend. Early and effective predictors of clinical outcomes is urgent needed to improve management of Covid‐19 patients. OBJECTIVE: The aim of the present study was to evaluate whether elevated D‐dimer levels could predict mortality in patients with Covid‐19. METHODS: Patients with laboratory confirmed Covid‐19 were retrospective enrolled in Wuhan Asia General Hospital from January 12, 2020 to March 15, 2020. D‐dimer levels on admission, and death events were collected to calculate the optimum cutoff using receiver operating characteristic curve. According to the cutoff, the subjects were divided into two groups. Then the in‐hospital mortality between two groups were compared to assess the predictive value of D‐dimer level. RESULTS: A total of 343 eligible patients were enrolled in the study. The optimum cutoff value of D‐dimer to predict in‐hospital mortality was 2.0 µg/ml with a sensitivity of 92.3% and a specificity of 83.3%. There were 67 patients with D‐dimer≥2.0 µg/ml, and 267 patients with D‐dimer <2.0 µg/ml on admission. 13 deaths occurred during hospitalization. Patients with D‐dimer levels≥2.0 µg/ml had a higher incidence of mortality when comparing to those who with D‐dimer levels < 2.0 µg/ml (12/67 vs 1/267, P<0.001, HR:51.5, 95%CI:12.9‐206.7). CONCLUSIONS: D‐dimer on admission greater than 2.0µg/mL (fourfold increase) could effectively predict in‐hospital mortality in patients with Covid‐19, which indicated D‐dimer could be an early and helpful marker to improve management of Covid‐19 patients.

positive: Alpha-1 adrenergic receptor antagonists for preventing acute respiratory distress syndrome and death from cytokine storm syndrome. In severe viral pneumonias, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists ($\alpha$-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia (n = 13,125 and n = 108,956, respectively) from all causes; patients who were incidentally taking $\alpha$-blockers had a reduced risk of requiring ventilation (by 35% and 16%, respectively), and a reduced risk of being ventilated and dying (by 56% and 20%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects. These results highlight the urgent need for prospective trials testing whether prophylactic $\alpha$-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.

positive: Immune dysfunction leads to mortality and organ injury in patients with COVID-19 in China: insights from ERS-COVID-19 study

positive: 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.

positive: 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.

positive: Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019 Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a cluster of coronavirus disease 2019 (COVID-19). We reported the clinical characteristics of COVID-19 patients with acute respiratory distress syndrome (ARDS), and further investigated the treatment and progression of ARDS in COVID-19. Methods: This study enrolled 109 patients with COVID-19 admitted to the Central Hospital of Wuhan, a designated hospital in Wuhan, China, from January 2 to February 1, 2020. Patients were followed up to February 12, 2020. The clinical data were collected from the electronic medical records. The differences in the treatment and progression with the time and the severity of ARDS were determined. Findings: Among 109 patients, mean age was 55 years, and 59 patients were male. With a median 15 days (range, 4 to 30 days) follow-up period, 31 patients (28.4%) died, while 78 (71.6%) survived and discharged. Of all patients, 53 (48.6%) developed ARDS. Compared to non-ARDS patients, ARDS patients were elder (mean age, 61 years vs. 49 years), and more likely to have the coexistent conditions, including diabetes (20.8% vs. 1.8%), cerebrovascular disease (11.3% vs. 0%), and chronic kidney disease (15.1% vs. 3.6%). Compared to mild ARDS patients, those with moderate and severe ARDS had higher mortality rates. No significant effect of antivirus, glucocorticoid, or immunoglobulin treatment on survival was observed in patients with ARDS. Interpretation: The mortality rate increased with the severity of ARDS in COVID-19, and the effects of current therapies on the survival for these patients were not satisfactory, which needs more attention from clinicians. Funding: Health and Family Planning Commission of Wuhan Municipality.

positive: Estimating the Risks from COVID-19 Infection in Adult Chemotherapy Patients The SARS-CoV-2 (COVID-19) novel coronavirus represents a significant health risk, particularly in older patients. Cancer is one of the leading causes of death in most rich countries, and delivering chemotherapy may be associated with increased risk in the presence of a pandemic infection. Estimating this risk is crucial in making decisions about balancing risks and benefits from administering chemotherapy. However, there are no specific data about chemotherapy risks per se. Here we develop a simple model to estimate the potential harms in patients undergoing chemotherapy during a COVID outbreak. We use age-related case fatality rates as a basis for estimating risk, and use previous data from risk of death during influenza outbreaks to estimate the additional risk associated with chemotherapy. We use data from randomised trials to estimate benefit across a range of curative and palliative settings, and address the balance of benefit against the risk of harm. We then use those data to estimate the impact on national chemotherapy delivery patterns.

positive: Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

positive: A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice No single animal model for severe acute respiratory syndrome (SARS) reproduces all aspects of the human disease. Young inbred mice support SARS-coronavirus (SARS-CoV) replication in the respiratory tract and are available in sufficient numbers for statistical evaluation. They are relatively inexpensive and easily accessible, but their use in SARS research is limited because they do not develop illness following infection. Older (12- to 14-mo-old) BALB/c mice develop clinical illness and pneumonitis, but they can be hard to procure, and immune senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen passages resulted in a virus (MA15) that is lethal for mice following intranasal inoculation. Lethality is preceded by rapid and high titer viral replication in lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral antigen is extensively distributed in bronchial epithelial cells and alveolar pneumocytes, and necrotic cellular debris is present in airways and alveoli, with only mild and focal pneumonitis. These observations suggest that mice infected with MA15 die from an overwhelming viral infection with extensive, virally mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus has six coding mutations associated with adaptation and increased virulence; when introduced into a recombinant SARS-CoV, these mutations result in a highly virulent and lethal virus (rMA15), duplicating the phenotype of the biologically derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of disease seen in severe human cases of SARS. The availability of the MA15 virus will enhance the use of the mouse model for SARS because infection with MA15 causes morbidity, mortality, and pulmonary pathology. This virus will be of value as a stringent challenge in evaluation of the efficacy of vaccines and antivirals.

positive: Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: a modelling study in Hubei, China and northern Italy Background. The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Wuhan, China in late 2019 is now pandemic. Reliable estimates of death from coronavirus disease 2019 (COVID-19) are essential to guide control efforts and to plan health care system requirements. The objectives of this study are to: 1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data; 2) give estimates of SARS-CoV-2 mortality adjusted for bias in the two regions with the world's highest numbers of confirmed Covid-19 deaths: Hubei province, China and northern Italy. Method and Findings. We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases; preferential ascertainment of severe cases and delayed mortality (right-censoring). We fitted our transmission model to surveillance data from Hubei province (1 January to 11 February 2020) and northern Italy (8 February to 3 March 2020). Overall mortality among all symptomatic and asymptomatic infections was estimated to be 3.0% (95% credible interval: 2.6-3.4%) in Hubei province and 3.3% (2.0-4.7%) in northern Italy. Mortality increased with age; we estimate that among 80+ year olds, 39.0% (95%CrI: 31.1-48.9%) in Hubei province and 89.0% (95%CrI: 56.2-99.6%) in northern Italy dies or will die. Limitations are that the model requires data recorded by date of onset and that sex-disaggregated mortality was not available. Conclusions. We developed a mechanistic approach to correct the crude CFR for bias due to right-censoring and preferential ascertainment and provide adjusted estimates of mortality due to SARS-CoV-2 infection by age group. While specific to the situation in Hubei, China and northern Italy during these periods, these findings will help the mitigation efforts and planning of resources as other regions prepare for SARS-CoV-2 epidemics.

positive: The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

positive: Clinical characteristics and outcomes of cancer patients with COVID-19 This retrospective study aimed to analysis clinical characteristics and outcomes of cancer patients with novel coronavirus disease-19 (COVID-19). Medical records, laboratory results and radiologic findings of 52 cancer patients with COVID-19 were collected, clinical characteristics and outcomes were summarized. A total of 52 cancer patients with COVID-19 were included. Median age of 52 cancer patients with COVID-19 was 63 years (34-98). Thirty-three (63.5%) patients were mild and 19 (36.5%) were severe/critical. Lung cancer was the most frequent cancer type (10, 19.2%). The common symptoms were as follows: fever (25%), dry cough (17.3%), chest distress (11.5%), and fatigue (9.6%). There were 33 (63.5%) patients had comorbidities, the most common symptom was hypertension (17, 51.5%). Twenty-six (78.8%) patients developed pneumonia on admission. Lymphocytes (0.6 × 109/L) decreased in both mild and severe/critical patients. Median levels of D-dimer, C-reactive protein, procalcitonin, and lactate dehydrogenase were 2.8 mg/L, 70.5 mg/L, 0.3 ng/mL, and 318 U/L, respectively, which increased significantly in severe/critical patients compared with the mild patients. Interleukin-6 (12.6 pg/mL) increased in both mild and severe/critical patients, there was a significant difference between them. Complications were observed in 29 (55.8%) patients, such as liver injury (19, 36.5%), acute respiratory distress syndrome (9, 17.3%), sepsis (8, 15.4%), myocardial injury (8, 15.4%), renal insufficiency (4, 7.7%), and multiple organ dysfunction syndrome (3, 5.8%). Eleven (21.2%) patients with cancer died. The infection rate of severe acute respiratory syndrome coronavirus 2 in patients with cancer was higher than the general population, cancer patients with COVID-19 showed deteriorating conditions and poor outcomes.

positive: Encountering COVID-19 as Endocrinologists The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.

positive: Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

positive: COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don’t

positive: The silent deaths of the elderly in long-term care facilities during the Covid-19 pandemic: The role of forensic pathology The Covid-19 pandemic is currently a major global public health problem. We know that the elderly and people with chronic diseases contract the infection more easily and they develop clinically more serious and often lethal forms. To date, the reasons for this have been generically attributed to old age and underlying diseases. Most Covid-19 deaths occurred in long-term care facilities because the residents are elderly people with chronic illness living in close contact. Therefore, facilities have become epidemic outbreaks. Forensic knowledge is very limited because an autopsy is rarely performed. Post-mortem investigations can help increase knowledge about Covid-19 and identify any undiagnosed pathologies in life. Therefore, forensic investigations play a role in protecting a frail population. Autopsies should be encouraged on elderly people who died of Covid-19.

positive: COVID-19: what if the brain had a role in causing the deaths?

positive: Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS: We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS: 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS: There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.

positive: COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome Background: Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS) is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility. Methods: We performed detailed flow cytometric analysis of peripheral blood samples from 28 COVID-19 patients treated at Xian No.8 Hospital and the First Affiliated Hospital of Xian Jiaotong University in early 2020 in an attempt to identify factors that could help predict severity of disease and patient outcome. Findings: While we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals,we did identify significant morphological and functional differences, which are more pronounced in patients requiring prolonged hospitalization and ICU admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter, side scatter analysis by routine flow cytometry,with the presence of a distinct population of monocytes with high forward scatter (FSC-high). On more detailed analysis, these FSC-high monocytes are CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, CD206+ and secrete IL-6, IL-10 and TNF-alpha, consistent with an inflammatory phenotype. Conclusions: The detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation.

positive: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 µg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) ï»¿may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.

positive: Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study Background: Since December 2019, when coronavirus disease 2019 (COVID 19) emerged in Wuhan and rapidly spread throughout the world, critically ill patients have a high mortality rate. We aimed to assess the effect of continuous renal replacement therapy (CRRT) on all cause mortality in patients with COVID 19 undergoing invasive mechanical ventilation. Methods: In this retrospective cohort study, we included all patients with COVID 19 undergoing invasive mechanical ventilation at Optical Valley Branch of Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan from February 12th to March 2nd, 2020. Demographic, clinical, laboratory, and treatment data were collected and analyzed. All patients were followed until death or end of follow up (March 9th), and all survivors were followed for at least one week. Findings: Of 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 (SD 1.8) years and 30 (83.3%) were men. 22 (61.1%) patients received CRRT (CRRT group) and 14 cases (38.9%) were managed in conventional strategy (non CRRT group). There was no difference in age, sex, comorbidities, complications, treatments and most of the laboratory findings, except for patients in the CRRT group with higher levels of aspartate aminotransferase and serum creatinine. During the average follow-up period of 10.4 days, 12 of 22 (54.5%) patients in CRRT group and 11 of 14 (78.6%) patients in non CRRT group died. Kaplan Meier analysis demonstrated a prolonged survival in patients in CRRT group than non CRRT group (P=0.032). The association between CRRT treatment and a reduced risk of mortality remained significant after adjusting for confounding factors in seven different models, with an adjusted hazard ratio (aHR) varying between 0.283 and 0.424. Older age, higher levels of IL1b, IL2 receptor, hs cTnI and NT proBNP were independently associated with increased risk of mortality in patients with CRRT treatment. Interpretation: CRRT may be beneficial for the treatment of COVID 19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.

positive: Concomitant brain arterial and venous thrombosis in a COVID‐19 patient COVID‐19 infection can cause a severe pneumonia which, in some cases, can lead to admission in intensive care unit for respiratory support.(1) In severe cases, systemic thrombotic complication has been described, including cerebrovascular disease (5.7‐23% of cases).(2,3)

positive: Myocardial injury is associated with higher mortality in patients with coronavirus disease 2019: a meta-analysis

positive: 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.

positive: 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.

positive: Early evidence of pronounced brain involvement in fatal COVID-19 outcomes

positive: Comparison of the Clinical Implications among Two Different Nutritional Indices in Hospitalized Patients with COVID-19 Background: Coronavirus disease 2019 (COVID 19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID 19. Methods: In this retrospective single center study, we finally included 245 consecutive patients who confirmed COVID 19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death . Results: 212 of them were discharged and 33 of them died. In hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe CONUT group than in the moderate, mild , and normal CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124 10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI(0.581 0.896),P=0.003) were independent predictors of all cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in hospital death(odds ratio 24.225, 95% CI(2.147 273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI(0.644 0.862);respectively).The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI(0.686 0.809); respectively).We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID 19 patients. Conclusion:The CONUT score and PNI could be a reliable prognostic marker of all cause death in patients with COVID 19. Keywords: Coronavirus disease 2019; nutrition; indicies; prognosis

positive: Abnormal liver function tests predict transfer to intensive care unit and death in COVID-19 BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19. METHODS: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID-19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.

positive: COVID-19 infection may cause ketosis and ketoacidosis The present study included 658 hospitalized patients with confirmed COVID-19. Forty-two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0-70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8-33.3] vs. 16.0 [10.0-24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non-diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID-19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.

positive: Comorbidities and multi-organ injuries in the treatment of COVID-19

positive: Cardiovascular comorbidities and complications associated with coronavirus disease 2019 Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.

positive: Clinical characteristics and risk factors for mortality among inpatients with COVID‐19 in Wuhan, China

positive: Cardiac injuries in patients with coronavirus disease 2019: Not to be ignored Abstract Objective To describe the clinical features of coronavirus disease 2019 (COVID-19). Methods We recruited 73 patients with COVID-19 [49 men and 24 women; average age: 58.36 years (SD: 14.31)] admitted to the intensive care unit of Wuhan Jinyintan Hospital from December 30, 2019 to February 16, 2020. Demographics, underlying diseases, and laboratory test results on admission were collected and analyzed. Data were compared between survivors and non-survivors. Results The non-survivors were older (65.46 [SD 9.74] vs 46.23 [12.01]) and were more likely to have chronic medical illnesses. Non-survivors tend to develop more severe lymphopenia, with higher C-reactive protein, interleukin-6, D-dimer, and hs-Troponin I(hs-TnI) levels. Patients with elevated hs-TnI levels on admission had shorter duration from symptom onset to death. Increased hs-TnI level was related to dismal prognosis. Death risk increased by 20.8% when the hs-TnI level increased by one unit. After adjusting for inflammatory or coagulation index, the independent predictive relationship between hs-TnI and death disappeared. Conclusions Cardiac injury may occur at the early stage of COVID-19, which is associated with high mortality. Inflammatory factor cascade and coagulation abnormality may be the potential mechanisms of COVID-19 combined with cardiac injury.

positive: Predictors of mortality in hospitalized COVID‐19 patients: A systematic review and meta‐analysis Mortality rates of coronavirus disease 2019 (COVID‐19) continue to rise across the world. Information regarding the predictors of mortality in COVID‐19 patients remains scarce. Herein, we performed a systematic review of published articles, from January 1 to April 24, 2020, to evaluate the risk factors associated with mortality in COVID‐19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (OR 2.5; 95% CI 2.1‐3.1; P<0.00001), coronary heart disease (OR 3.8; 95% CI 2.1‐6.9; P<0.00001) and diabetes (OR 2.0; 95% CI 1.7‐2.3; P<0.00001) were associated with significantly higher risk of death amongst COVID‐19 patients. Those who died, compared to those who survived, differed on multiple biomarker levels on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI 19.0‐69.4; P=0.0006); C‐reactive protein (+66.3 µg/mL, 95% CI 46.7‐85.9; P<0.00001); interleukin‐6 (+4.6 ng/mL, 95% CI 3.6‐5.6; P<0.00001); D‐dimer (+4.6 µg/mL, 95% CI 2.8‐6.4; P<0.00001); creatinine (+15.3 µmol/L, 95% CI 6.2‐24.3; P=0.001) and alanine transaminase (+5.7 U/L, 95% CI 2.6‐8.8; P=0.0003); as well as decreased levels of albumin (‐3.7 g/L, 95% CI ‐5.3 to ‐2.1; P<0.00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end‐organ damage are at higher risk of mortality due to COVID‐19 infection and should be managed with greater intensity. This article is protected by copyright. All rights reserved.

positive: Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7-13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

positive: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020 Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19-associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12-March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities (4). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups.

positive: [Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man]. In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.

positive: SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications Abstract The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world – this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death. To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease. Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body. The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization. We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.

positive: 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.

positive: Molecular mechanisms for thrombosis risk in Black people: a role in excess mortality from COVID‐19 We read with interest your recent article by Fogarty et al, in particular their conclusion that differences in thrombotic risk may contribute to ethnic disparities in mortality from Covid-19.(1) This is especially important in the UK, where age-sex adjusted hospital death rates for Covid-19 are 2.17 times higher for people with ethnicity recorded as black compared to those recorded as white, and 1.95 higher for those recorded as Asian.(2) This excess mortality persists after adjustment for deprivation, body mass index (BMI), smoking and comorbidities,(2) and despite correction for region, rural or urban living, deprivation, household composition, socioeconomic status, and health.(3) Similar data from the USA shows that in 14 states, African-Americans represent 33% of hospitalisations for Covid-19, despite only making up 14% of the catchment population.(4) Black ethnicity is a construct incorporating diverse populations of African descent. Studies from several communities labelled as black, in particular African-Americans, imply a common increase in thrombotic risk, which may contribute to unexplained ethnic disparities in the UK and USA in Covid-19.

positive: Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06010-9) contains supplementary material, which is available to authorized users.

positive: Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase “acute respiratory distress syndrome” (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.

positive: [Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man] In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure A chest X-ray showed signs of acute respiratory distress syndrome Despite aggressive intensive care management, the patient died 7 5 hours after admission Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea

positive: Epidemiologie von SARS-CoV-2-Infektion und COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new β‑Coronavirus that was first detected in 2019 in Wuhan, China. In the ensuing months it has been transmitted worldwide. Here the authors present the current knowledge on the epidemiology of this virus. SARS-CoV‑2 replicates mainly in the upper and lower respiratory tract and is primarily transmitted by droplets from asymptomatic and symptomatic infected subjects. The estimate for the basic reproduction number (R) is currently between 2 and 3, while the incubation period is 6 (median, range 2–14) days. Although most infections are uncomplicated, 5–10% of cases develop pneumonia, which can lead to hospitalization, respiratory failure and multiorgan failure. Risk factors for a complicated disease course include age, hypertension, chronic cardiovascular and pulmonary disease and immunodeficiency. The overall case fatality rate is 1.4%, with the rate rising in the sixth decade of life. Nosocomial and infections in medical personnel have been reported. Drastic reductions in social contact have been implemented in many countries with outbreaks of SARS-CoV‑2, leading to rapid reductions in R. Which of the measures have been effective is still unknown.

positive: 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.

positive: COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study BACKGROUND: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. METHODS: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. FINDINGS: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56-10·02]; p<0·0001), being male (1·67 [1·19-2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36-2·80]; p<0·001) and cardiovascular disease (2·32 [1·47-3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81-1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. INTERPRETATION: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. FUNDING: University of Birmingham, University of Oxford.

positive: Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1 BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses. RESEARCH QUESTION: The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS. STUDY DESIGN AND METHODS: This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared. RESULTS: The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001). INTERPRETATION: There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

positive: 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.

positive: Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages BACKGROUND: Information about the clinical characteristics and mortality of patients with coronavirus disease 2019 at different ages is limited. RESULTS: The older group had more patients with dyspnea and fewer patients with fever and muscle pain. Older patients had more underlying diseases, secondary infection, myocardial injury, renal dysfunction, coagulation dysfunction, and immune dysfunction on admission. More older patients received immunoglobulin therapy and mechanical ventilation. The proportions of patients with multiple organ injuries, critically ill patients and death increased significantly with age. The older groups had higher cumulative death risk than the younger group. Hypertension, cerebrovascular disease, comorbidities, acute cardiac injury, shock and complications are independent predictors of death. CONCLUSIONS: The symptoms of the elderly patients were more atypical, with more comorbidities, secondary infection, organ injuries, immune dysfunction and a higher risk of critical illness. Older age was an important risk factor for mortality. METHODS: 1000 patients diagnosed with coronavirus disease 2019 from January 1, 2020 to February 14, 2020 were enrolled. According to age, patients were divided into group 1 (<60 years old), group 2 (60-74 years old) and group 3 (≥75 years old). The clinical symptoms, first laboratory results, CT findings, organ injuries, disease severity and mortality were analyzed.

positive: High mortality in COVID-19 patients with mild respiratory disease INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 189 000 people in Italy, with more than 25 000 deaths. Several predictive factors of mortality have been identified; however, none has been validated in patients presenting with mild disease. METHODS: Patients with a diagnosis of interstitial pneumonia caused by SARS-CoV-2, presenting with mild symptoms, and requiring hospitalization in a non-intensive care unit with known discharge status were prospectively collected and retrospectively analysed. Demographical, clinical and biochemical parameters were recorded, as need for non-invasive mechanical ventilation and admission in intensive care unit. Univariate and multivariate logistic regression analyses were used to identify independent predictors of death. RESULTS: Between 28 February and 10 April 2020, 229 consecutive patients were included in the study cohort; the majority were males with a mean age of 60 years. 54% of patients had at least one comorbidity, with hypertension being the most commonly represented, followed by diabetes mellitus. 196 patients were discharged after a mean of 9 days, while 14.4% died during hospitalization because of respiratory failure. Age higher than 75 years, low platelet count (<150 × 103 /mm3 ) and higher ferritin levels (>750 ng/mL) were independent predictors of death. Comorbidities were not independently associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality of patients with COVID-19 presenting with mild symptoms is high and is associated with older age, platelet count and ferritin levels. Identifying early predictors of outcome can be useful in the clinical practice to better stratify and manage patients with COVID-19.

positive: A Case Report of Rapidly Lethal Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019 Viral Pneumonia As of April 2020, the coronavirus 2019 (COVID-19) pandemic has resulted in more than 210,000 deaths globally. The most common cause of death from COVID-19 is acute respiratory failure. We report the case of a 78-year-old female with a history of hypertension, cerebrovascular accident (CVA), type 2 diabetes mellitus, and sarcoidosis, who presented to the emergency department with one day of dyspnea. The patient experienced a rapid decline in respiratory function and was intubated in the intensive care unit (ICU), meeting the Berlin criteria for severe acute respiratory distress syndrome (ARDS). Chest radiography revealed diffuse bilateral coalescent opacities, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA swab test was positive for COVID-19. The patient experienced acute kidney injury with uptrending creatinine levels and remained lethargic and unresponsive throughout her ICU stay, suggestive of potential hypoxic brain injury. In light of the patient’s poor clinical status, age, and significant comorbidities, prognosis was conveyed about medical futility and patient’s family agreed to terminal extubation and the patient expired peacefully, exactly one week from hospital admission. This case report highlights the speed at which severe ARDS can present and contribute to end-organ dysfunction in COVID-19 patients.

positive: Health status of patients with Autoimmune Liver Disease during SARS-CoV-2 outbreak in northern Italy

positive: Maternal Mortality From Coronavirus Disease 2019 (COVID-19) in the United States. Individual state maternal mortality review committees aim to comprehensively review all maternal deaths to not only evaluate the cause of death, but also to assess preventability and make recommendations for action to prevent future deaths. The maternal mortality review committee process remains critical during the coronavirus disease 2019 (COVID-19) pandemic. Maternal deaths due to COVID-19 have been reported in the United States. Some state maternal mortality review committees may choose to expedite review of these deaths in an effort to quickly provide clinicians with information intended to prevent other deaths during the ongoing pandemic. If states opt to pursue rapid review, entry of data into the Maternal Mortality Review Information Application system for submission to the Centers for Disease Control and Prevention will allow for aggregation nationally without duplication. It will be important to review not only deaths directly attributed to COVID-19, but also those that may be indirectly related to the COVID-19 pandemic, such as those influenced by changes in care practices or delays in seeking care during the pandemic. Therefore, regardless of the timing of the review, maternal deaths that occur during the time of the COVID-19 pandemic must be evaluated within that framework to ensure that all factors contributing to the death are considered to better understand the context of each of these tragic events.

positive: Clinical Characteristics of Coronavirus Disease 2019 in Hainan, China Background: Since January 2020, coronavirus disease 2019 (Covid-19) has spread rapidly and developing the pandemic model around the world. Data have been needed on the clinical characteristics of the affected patients in an imported cases as model in island outside Wuhan. Methods: We conducted a retrospective study included all 168 confirmed cases of Covid-19 in Hainan province from 22 January 2020 to 13 March 2020. Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, radiological and laboratory data. Results: Of 168 patients, 160 have been discharged, 6 have died and 2 remain hospitalized. The median age was 51.0 years and 51.8% were females. 129 (76.8%) patients were imported cases, and 118 (70.2%), 51 (30.4%) and 52 (31%) of patients lived in Wuhan or traveled to Wuhan, had contact with Covid-19 patients, or had contact with Wuhan residents, respectively. The most common symptoms at onset of illness were fever (65.5%), dry cough (48.8%) and expectoration (32.1%). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (60.2%). The elderly people with diabetes, hypertension and CVD are more likely to develop severe cases. Follow-up of 160 discharged patients found that 20 patients (12.5%) had a positive RT-PCR test results of pharyngeal swabs or anal swabs or fecal. Conclusions: In light of the rapid spread of Covid-19 around the world, early diagnosis and quarantine is important to curb the spread of Covid-19 and intensive treatments in early stage is to prevent patients away from critical condition.

positive: 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.

positive: Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis Background: Early descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK. Methods: We conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death. Findings: We identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 - 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 - 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 - 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations. Interpretation: These results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.

positive: Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography. AIMS Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. METHODS AND RESULTS This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I > 20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO/FiO ratio on admission were other independent predictors for both myocardial injury and death. CONCLUSIONS An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death. TRANSLATIONAL PERSPECTIVE The present study identifies myocardial injury as a clinically relevant independent risk factor for death in the short term in a population of hospitalized patients with laboratory-confirmed COVID-19 outside of China undergoing chest computed tomography for suspected pneumonia on admission.The study also provides novel insights into the risk factors for myocardial injury, showing that an increased pulmonary artery diameter, assessed by chest computed tomography, is an independent predictor of myocardial injury as well as of mortality, suggesting that pulmonary circulation dysfunction is a pivotal pathological event with cardiac implications in COVID-19.

positive: Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.

positive: Sudden death due to acute pulmonary embolism in a young woman with COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease that primarily affects the respiratory system, but it may cause cardiovascular complications such as thromboembolism. Rarely, pulmonary embolism may be encountered in patients with severe COVID-19 infection, especially in intensive care units. An asymptomatic young case of COVID-19 presenting with sudden death due to acute massive pulmonary embolism has not been previously described. We report a 41-year-old woman presented to emergency department with sudden death during physical activity. She had only history of diabetes mellitus and she was asymptomatic until sudden death. CT pulmonary angiography and chest CT scans revealed acute massive embolism and typical imaging findings of COVID-19 pneumonia, respectively. Interestingly, the patient had no symptoms or signs of infection and also had no risk factors for thromboembolism. COVID-19 infection appears to induce venous thromboembolism, especially pulmonary embolism. The case is remarkable in terms of showing how insidious and life-threatening COVID-19 infection can be.

positive: Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China Abstract Objectives 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 radiological 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. Results 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, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.

positive: COVID-19 pandemic: do we need systematic screening of patients with cardiovascular risk factors in Low and Middle-Income Countries (LMICs) for preventing death? COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.

positive: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/μL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] μg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] μg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.

positive: How Could This Happen? : Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS) In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.

positive: Tissue-specific tolerance in fatal Covid-19 Successful host defence against a pathogen can involve resistance or tolerance, with implications for prioritising either antimicrobial or immunomodulatory therapeutic approaches. Hyper-inflammation occurs in Covid-19 and is associated with worse outcomes. The efficacy of dexamethasone in preventing mortality in critical Covid-19 suggests that inflammation has a causal role in death. Whether this deleterious inflammation is primarily a direct response to the presence of SARS-CoV-2 requiring enhanced resistance, or an independent immunopathologic process necessitating enhanced tolerance, is unknown. Here we report an aberrant immune response in fatal Covid-19, principally involving the lung and reticuloendothelial system, that is not clearly topologically associated with the virus, indicating tissue-specific tolerance of SARS-CoV-2. We found that inflammation and organ dysfunction in fatal Covid-19 did not map to the widespread tissue and cellular distribution of SARS-CoV-2 RNA and protein, both between and within tissues. A monocyte/myeloid-rich vasculitis was identified in the lung, along with an influx of macrophages/monocytes into the parenchyma. In addition, stereotyped abnormal reticulo-endothelial responses (reactive plasmacytosis and iron-laden macrophages) were present and dissociated from the presence of virus in lymphoid tissues. Our results support virus-independent immunopathology being one of the primary mechanisms underlying fatal Covid-19. This supports prioritising pathogen tolerance as a therapeutic strategy in Covid-19, by better understanding non-injurious organ-specific viral tolerance mechanisms and targeting aberrant macrophage and plasma cell responses.

positive: Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also discussed the indirect immune response caused by SARS and direct infection, replication, and destroying of immune cells by MERS-CoV. The molecular mechanisms of SARS-CoV and MERS-CoV infection-induced lymphopenia or cytokine storm may provide some hint toward fight against SARS-CoV-2, the novel coronavirus. This may provide guidance over using immune therapy as a combined treatment to prevent patients developing severe respiratory syndrome and largely reduce complications.

positive: Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality Since December 2019, a viral pneumonia, named coronavirus disease 2019 (COVID-19), from Wuhan, China, has swept the world. Although the case fatality rate is not high, the number of people infected is large and there is still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. Therefore, treatment of the cytokine storm has become an important part of rescuing severe COVID-19 patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome. If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19.

positive: Kidney disease is associated with in-hospital death of patients with COVID-19 In December 2019, a coronavirus 2019 (COVID-19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID-19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID-19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID-19. This was a prospective cohort study of 701 patients with COVID-19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1%) died in hospital. Median age of the patients was 63 years (interquartile range, 50-71), including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1%, respectively. During the study period, AKI occurred in 5.1% patients. Kaplan-Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36-3.26), elevated baseline blood urea nitrogen (3.97, 2.57-6.14), AKI stage 1 (1.90, 0.76-4.76), stage 2 (3.51, 1.49-8.26), stage 3 (4.38, 2.31-8.31), proteinuria 1+ (1.80, 0.81-4.00), 2+∼3+ (4.84, 2.00-11.70), and hematuria 1+ (2.99, 1.39-6.42), 2+∼3+ (5.56,2.58- 12.01) were independent risk factors for in-hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID-19 is high and is associated with in-hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID-19.

positive: A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Abstract The SARS-CoV-2 epidemic is pressuring health care systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID task force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70) and dyspnea at presentation were associated with the risk of developing ARDS whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis.

positive: Epidemiological and clinical features of 200 hospitalized patients with corona virus disease 2019 outside Wuhan, China: A descriptive study BACKGROUND: The recent outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide, with especially severe epidemics occurring in cities across China. OBJECTIVES: To report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. STUDY DESIGN: 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8, 2020 were investigated retrospectively. The epidemiological data and clinical characteristics were collected. The data between the ICU patients and non-ICU patients were compared. The patients were followed up till Feb 26, 2020. RESULTS: Of the 200 hospitalized patients with COVID-19, 98 (49.0 %) were male, and the mean age was 55 years. Eighty-seven (43.5 %) had no linkage to Wuhan or contact history. Familial clustering was found in 34 patients. Sixtyfive (32.5 %) suffered from chronic diseases. The common symptoms included fever (171[85.5 %]), cough (116[58.0 %]), and fatigue (64[32 %]). Most patients had lymphopenia. One hundred and seventy-two (86 %) patients showed typical imaging findings of viral pneumonia. Most patients received antiviral, antibiotic, and corticosteroid treatment. Compared with the non-ICU patients, 29 (14.5 %) patients in the ICU were older and more likely to show dyspnea and complications including ARDS. As of Feb 26, 15 (51.7 %) patients in the ICU had died. CONCLUSIONS: The COVID-19 infection was of clustering onset and can cause severe respiratory disease and even death. The mortality of ICU patients with COVID-19 was considerably high.

positive: Where are we with understanding of COVID-19? Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.

positive: [Logistic regression analysis of death risk factors of patients with severe and critical coronavirus disease 2019 and their predictive value]. OBJECTIVE To analyze the risk factors of death in patients with severe and critical coronavirus disease 2019 (COVID-19) and their predictive value. METHODS Using the clinical and epidemiological database of Yangtze River Shipping General Hospital in Wuhan, the clinical and epidemiological data of 105 patients with severe and critical COVID-19 from January to March in 2020 were collected. Multivariate unconditional Logistic regression method was used to analyze the death risk factors of patients during hospitalization. The receiver operating characteristic (ROC) curve was drawn according to the multivariate analysis results to construct a death prediction model; the prediction value of the model was analyzed. RESULTS The 105 patients with severe and critical COVID-19 were enrolled with 66 males (62.9%) and 39 females (37.1%). The age was (58.2±14.4) years old. Forty-two patients died in hospital and 63 survived. Among the dead patients, 69.0% (29/42) were male, and 78.6% (33/42) were over 60 years old. Compared with survival patients, the non-survival patients were older (years old: 59.2±12.5 vs. 51.2±11.4), and had more comorbidities, including coronary heart disease, hypertension, myocardial damage and thrombocytopenia (coronary heart disease: 33.3% vs. 11.1%, hypertension: 28.6% vs. 9.5%, myocardial damage: 73.8% vs. 11.1%, thrombocytopenia: 61.9% vs. 14.3%), and received more mechanical ventilation (92.9% vs. 44.4%), with significant differences (all P < 0.01). The variables of gender, age, basic diseases, mechanical ventilation and complications were included in the unconditional Logistic regression analysis, which showed that gender [odds ratio (OR) = 2.852, 95% confidence interval (95%CI) was 0.122-66.694], age (OR = 3.257, 95%CI was 0.466-18.584), coronary heart disease (OR = 7.337, 95%CI was 0.227-87.021), hypertension (OR = 5.517, 95%CI was 0.258-65.024) and concurrent myocardial damage (OR = 7.322, 95%CI was 0.278-95.020) and thrombocytopenia (OR = 3.968, 95%CI was 0.325-35.549) were independent risk factors for death in patients with severe and critical COVID-19 during hospitalization. According to the risk factors, the death prediction model was constructed and ROC curve was analyzed, which showed that the area under ROC curve (AUC) of death prediction model for predicting the mortality of patients with severe and critical COVID-19 during hospitalization was 0.804, the sensitivity was 83.8%, and the specificity was 82.3%. CONCLUSIONS Various risk factors are associated with the death of severe or critical COVID-19 patients, such as gender, age, basic diseases and complications. The death prediction model is constructed by gender, age, basic diseases with coronary heart disease and hypertension, concurrent myocardial damage and thrombocytopenia, which has certain predictive value for the death of patients with severe or critical COVID-19.

positive: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Importance: Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective: To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants: This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures: Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results: A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13â¯800] vs 5500 [4200-7400] cells/µL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] µg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] µg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance: Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.

positive: Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients BACKGROUND: The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a series of clinical symptoms and severe illnesses, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. METHODS: The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining was performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. FINDINGS: The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. INTERPRETATION: Infection of alveolar macrophage by SARS-CoV-2 might be drivers of the "cytokine storm", which might result in damages in pulmonary tissues, heart and lung, and lead to the failure of multiple organs . FUNDING: Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China.

positive: Thrombocytopenia and its association with mortality in patients with COVID-19 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease 2019 (COVID-19), is spreading rapidly around the world. Thrombocytopenia in patients with COVID-19 has not been fully studied. OBJECTIVE: To describe thrombocytopenia in patients with COVID-19. METHODS: For each of 1476 consecutive patients with COVID-19 from Jinyintan Hospital, Wuhan, China, nadir platelet count during hospitalization was retrospectively collected and categorized into (0, 50], (50, 100], (100-150], or (150-) groups after taking the unit (×109 /L) away from the report of nadir platelet count. Nadir platelet counts and in-hospital mortality were analyzed. RESULTS: Among all patients, 238 (16.1%) patients were deceased and 306 (20.7%) had thrombocytopenia. Compared with survivors, non-survivors were older, were more likely to have thrombocytopenia, and had lower nadir platelet counts. The in-hospital mortality was 92.1%, 61.2%, 17.5%, and 4.7% for (0, 50], (50, 100], (100-150], and (150-) groups, respectively. With (150-) as the reference, nadir platelet counts of (100-150], (50, 100], and (0, 50] groups had a relative risk of 3.42 (95% confidence interval [CI] 2.36-4.96), 9.99 (95% CI 7.16-13.94), and 13.68 (95% CI 9.89-18.92), respectively. CONCLUSIONS: Thrombocytopenia is common in patients with COVID-19, and it is associated with increased risk of in-hospital mortality. The lower the platelet count, the higher the mortality becomes.

positive: Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction. AIMS Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS This study reports autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. RESULTS The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolisms (n=4), alveolar haemorrhage (n=3) and vasculitis (n=1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS This study provides an overview of post-mortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates amongst these patients.

positive: 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.

positive: Clinical considerations for patients with diabetes in times of COVID-19 pandemic

positive: Clinical features of familial clustering in patients infected with 2019 novel coronavirus in Wuhan, China An epidemic caused by SARS-Coronavirus-2 (SARS-CoV-2) infection has appeared in Wuhan City in December 2019 and subsequently spread in China. The disease has shown a "clustering epidemic" pattern, and family-clustered onset has been the main characteristic. We collected data from 130 cases from 35 cluster-onset families (COFs) and 41 cases from 16 solitary-onset families (SOFs). The incidence 2019 coronavirus disease (COVID-19) in COFs was significantly higher than that of SOFs. Our study also showed that patients with exposure to high-risk factors (respiratory droplets and close contact), advanced age, and comorbidities were more likely to develop COVID-19 in the COFs. In addition, advanced age and elevated neutrophil/lymphocyte ratio (NLR) were risk factors for death in patients with SARS-CoV-2 infection in the COFs.

positive: Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Background: Cardiovascular diseases(CVD) increase mortality risk from coronavirus infection(COVID-19), but there are concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both direct, through infection, and indirect, through changes in healthcare. Methods: We used population-based electronic health records from 3,862,012 individuals in England to estimate pre- and post-COVID-19 mortality risk(direct effect) for people with incident and prevalent CVD. We incorporated: (i)pre-COVID-19 risk by age, sex and comorbidities, (ii)estimated population COVID-19 prevalence, and (iii)estimated relative impact of COVID-19 on mortality(relative risk, RR: 1.5, 2.0 and 3.0). For indirect effects, we analysed weekly mortality and emergency department data for England/Wales and monthly hospital data from England(n=2), China(n=5) and Italy(n=1) for CVD referral, diagnosis and treatment until 1 May 2020. Findings: CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy and England during the pandemic. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown, and is still reduced in Italy and England. Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous(peak RR 1.4). For total CVD(incident and prevalent), at 10% population COVID-19 rate, we estimated direct impact of 31,205 and 62,410 excess deaths in England at RR 1.5 and 2.0 respectively, and indirect effect of 49932 to 99865 excess deaths. Interpretation: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the COVID-19 pandemic.

positive: Thromboinflammation and the hypercoagulability of COVID-19. The pathogenic coronavirus has been wreaking havoc worldwide since January. Infection with SARS-CoV-2 is problematic as no one has prior immunity, and no specific antiviral treatments are available. While many people with COVID-19 develop mild to moderate symptoms, some develop profound seemingly unchecked inflammatory responses leading to acute lung injury and hypoxemic respiratory failure, the most common cause for death.

positive: Considerations for people with diabetes during the Coronavirus Disease (COVID-19) Pandemic INTRODUCTION: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of SARS-CoV-2 on people with diabetes. AIMS: (1) To characterise the outcomes of SARS-CoV-2 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management. METHODS: A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV in the context of diabetes. CONCLUSION: People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.

positive: The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China Abstract The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002–2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

positive: 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.

positive: Tabagisme et maladie à coronavirus 2019 (COVID-19)

positive: 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.

positive: Coronavirus Disease 2019 (Covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: a case report and literature review. The vast majority of patients in the ongoing coronavirus Disease 2019 (Covid-19) pandemic primarily present with severe respiratory illness. We report a Covid-19 patient who presented with findings of acute coronary syndrome and was found to have purulent fulminant myopericarditis and cardiac tamponade. We compare our case to the previously reported instances of Covid-19-associated myocarditis. Through review of the available literature, we also highlight the potential mechanisms of cardiac injury in Covid-19. We hope to increase awareness amongst clinicians about this unusual presentation of Covid-19.

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: [Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy] Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type â ¡ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type â ¡ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type â ¡ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.

positive: Clinical characteristics of 2019 novel coronavirus infection in China Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

positive: Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively. Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

positive: Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.

positive: Potential Factors for Prediction of Disease Severity of COVID-19 Patients Abstract: Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9+/-9.4 vs 44.4+/-15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. Conclusion: Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients. Keyword: COVID-19, erythrocyte sedimentation rate, cytokines, lymphocytes

positive: Gender Differences in Patients With COVID-19: Focus on Severity and Mortality Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

positive: Why does COVID-19 disproportionately affect older people? The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection and effectively regulate immune responses.

positive: Sudden cardiac death in COVID-19 patients, a report of three cases The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1-6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.

positive: Comparison of mortality associated with respiratory viral infections between December 2019 and March 2020 with that of the previous year, Southeastern France Abstract Respiratory viruses are a major global cause of mortality worldwide and in France where they cause several thousands of deaths yearly. University Hospital Institute-Méditerranée Infection performs real-time surveillance of all diagnoses of infections and associated deaths in public hospitals of Marseille, Southeastern France. Here, mortality associated with diagnoses of respiratory viruses was compared during colder months of 2018-2019 and 2019-2020 (week 47-week 14). In 2018-2019, 73 patients (0.17% of 42,851 hospitalized patients) died after being diagnosed with a respiratory virus; 40 and 13 deaths occurred in patients diagnosed with influenza A virus and respiratory syncytial virus (RSV), respectively. In 2019-2020, 50 patients (0.10% of 49,043 patients hospitalized) died after being diagnosed with a common respiratory virus; 7 and 7 deaths occurred in patients diagnosed with influenza A virus and RSV, respectively. Additionally, 55 patients died after being diagnosed with SARS-CoV-2. The proportion of respiratory virus-associated deaths among hospitalized patients was thus significantly lower for common respiratory viruses in 2019-2020 than in 2018-2019 (102 versus 170 per 100,000 hospitalized patients; p=0.003), majoritarily as a consequence of a decrease in influenza A virus (-83%) and RSV (-46%)-associated deaths. Overall, the proportion of respiratory virus-associated deaths among hospitalized patients was higher but not significantly in 2019-2020 than in 2018-2019 (214 versus 170 per 100,000 hospitalized patients; p=0.08, Yates-corrected chi-square test). These findings allow putting into perspective the death burden of SARS-CoV-2 infections in our geographical area.

positive: Association of age, sex, comorbidities, and clinical symptoms with the severity and mortality of COVID-19 cases: a meta-analysis with 85 studies and 67299 cases Background: A new pathogenic disease named COVID-19 became a global threat, first reported in Wuhan, China, in December 2019. The number of affected cases growing exponentially and now, more than 210 countries confirmed the cases. Objective: This meta-analysis aims to evaluate risk factors, the prevalence of comorbidity, and clinical characteristics in COVID-19 death patients compared to survival patients that can be used as a reference for further research and clinical decisions. Methods: PubMed, Science Direct, SAGE were searched to collect data about demographic, clinical characteristics, and comorbidities of confirmed COVID-19 patients from January 1, 2020, to May 17, 2020. Meta-analysis was performed with the use of Review Manager 5.3 Results: Eighty-five studies were included in Meta-analysis, including a total number of 67,299 patients with SARS-CoV-2 infection. Males are severely affected or died than females (OR = 2.26, p < 0.00001; OR = 3.59, p < 0.00001) are severely affected, or died by COVID-19 and cases with age [≥]50 are at higher risk of death than age <50 years (OR=334.23). Presence of any comorbidity or comorbidities like hypertension, cardiovascular disease, diabetes, cerebrovascular disease, respiratory disease, kidney disease, liver disease, malignancy significantly increased the risk of death compared to survival (OR = 3.46, 3.16, 4.67, 2.45, 5.84, 2.68, 5.62, 2.81,2.16). Among the clinical characteristics such as fever, cough, myalgia, diarrhea, abdominal pain, dyspnea, fatigue, sputum production, chest tightness headache and nausea or vomiting, only fatigue (OR = 1.31, 95%) and dyspnea increased the death significantly (OR= 1.31, 4.57). The rate of death of COVID-19 cases is 0.03-times lower than the rate of survival (OR = 0.03). Conclusion Our result indicates that male patients are affected severely or died, the rate of death is more in the age [≥]50 group, and the rate of death is affected by comorbidities and clinical symptoms.

positive: Cardiac injuries in patients with coronavirus disease 2019: Not to be ignored OBJECTIVE: To describe the clinical features of coronavirus disease 2019 (COVID-19). METHODS: We recruited 73 patients with COVID-19 [49 men and 24 women; average age: 58.36 years (SD: 14.31)] admitted to the intensive care unit of Wuhan Jinyintan Hospital from December 30, 2019 to February 16, 2020. Demographics, underlying diseases, and laboratory test results on admission were collected and analyzed. Data were compared between survivors and non-survivors. RESULTS: The non-survivors were older (65.46 [SD 9.74]vs 46.23 [12.01]) and were more likely to have chronic medical illnesses. Non-survivors tend to develop more severe lymphopenia, with higher C-reactive protein, interleukin-6, D-dimer, and hs-Troponin I(hs-TnI) levels. Patients with elevated hs-TnI levels on admission had shorter duration from symptom onset to death. Increased hs-TnI level was related to dismal prognosis. Death risk increased by 20.8% when the hs-TnI level increased by one unit. After adjusting for inflammatory or coagulation index, the independent predictive relationship between hs-TnI and death disappeared. CONCLUSIONS: Cardiac injury may occur at the early stage of COVID-19, which is associated with high mortality. Inflammatory factor cascade and coagulation abnormality may be the potential mechanisms of COVID-19 combined with cardiac injury.

positive: COVID-19 y enfermedad cardiovascular In December 2019, in Wuhan in the province of Hubei in China, there was a report on a group of 27 patients with a pneumonia of unknown origin, linked to exposure in a market with shellfish, fish, and live animals. In January 2020, a new strain of coronavirus (SARS-CoV-2) was isolated in these patients. The disease caused by this virus has been given the name of COVID-19. During the initial stages of the pandemic, and given the scarcity of studies published about this, it was believed that this coronavirus only caused respiratory symptoms. However, as the number of patients increased, it was observed that cardiovascular disease had a fundamental role in the development and prognosis of the infection. The most important risk factors associated with mortality are age and the presence of comorbidities, particularly cardiovascular ones. The increase in the levels of troponin, natriuretic peptides, and D-dimer are of prognostic values in patients with an infection due to SARS-CoV-2. Patients with COVID-19 have an increased risk of acute myocardial infarction, myocarditis, heart failure, shock, arrhythmias, and sudden death, in relation to the systematic response to the virus and to the treatments needed in the acute phase. A review is presented in this article of the cardiovascular involvement due to SARS-CoV-2 (COVID-19).

positive: AUTOPSIAS EN CASOS SOSPECHOSOS DE SARS-CoV-2 Resumen La medicina forense debe contemplar la posibilidad de que fallecidos por causas violentas o desconocidas puedan estar infectados por el virus SARS-CoV-2, o que el diagnóstico de la enfermedad tenga implicaciones legales, lo que exige un conocimiento adecuado de la epidemiología de la enfermedad, de las medidas de protección, de la toma de muestras y de las características anatomopatológicas. La práctica de autopsias en fallecidos por COVID-19 se ha visto limitada por las obligadas medidas preventivas frente al contagio y por la necesidad de disponer de instalaciones con nivel de protección frente a riesgos biológicos de nivel 3, de modo que las series publicadas hasta la fecha son escasas, y parciales, con abordajes limitados (autopsia mínimamente invasiva o biopsia con aguja gruesa). En este artículo se hace una revisión de los aspectos de la fisiopatología de la enfermedad que tienen repercusión en la infectividad de los tejidos y fluidos del cadáver, de las medidas de prevención del riesgo biológico, de la toma de muestras y de los hallazgos patológicos, tanto macroscópicos como microscópicos, asociados a la muerte provocada por la infección por el virus SARS-CoV-2. Abstract Forensic physicians should consider the possibility that people who have died from violent or unknown causes may be infected by the virus SARS-CoV-2, or that the diagnosis of the disease has legal implications, which requires adequate knowledge of the epidemiology of the disease, protective measures, adequate sampling and the pathological characteristics. The practice of autopsies on people who have died from COVID-19 has been limited by the mandatory preventive measures against contagion and by the need for facilities with a level of protection against level-3 biological risk, and therefore series published to date are scarce and partial,with limited approaches (minimally invasive autopsy or needle biopsy). This article reviews the aspects of the pathophysiology of the disease that have an impact on the infectivity of the body's tissues and fluids, measures for preventing biological risk, taking samples and pathological findings, both macroscopic and microscopic, associated with death caused by infection with the SARS-CoV-2 virus.

positive: 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.

positive: 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.

positive: Coronavirus Disease (COVID-19) in Italy: Analysis of Risk Factors and Proposed Remedial Measures

positive: 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.

positive: Autopsy findings from the first known death from Severe Acute Respiratory Syndrome SARS-CoV-2 in Spain The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. We present the relevant autopsy findings of the first patient known to have died from COVID19 pneumonia in Spain, carried out on the 14th of February, 2020, in our hospital (Hospital Arnau de Vilanova-Lliria, Valencia). Histological examination revealed typical changes of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present. The diagnosis was confirmed by reverse real-time PCR assay on a throat swab sample taken during the patient's admission. The positive result was reported fifteen days subsequent to autopsy.

positive: COVID‐19 infection may cause ketosis and ketoacidosis The present study included 658 hospitalized patients with confirmed COVID‐19. Forty‐two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0–70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8–33.3] vs. 16.0 [10.0–24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non‐diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID‐19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.

positive: Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients To confirm the relationship between sex and the progression of Coronavirus Disease-19 (COVID-19), and its potential mechanism, among severe patients. For this retrospective study, we included 168 consecutive severe patients with pathogen-confirmed COVID-19 who were hospitalized between January 16th and February 4th, 2020, at Tongji Hospital in Wuhan, China. Clinical characteristics, laboratory parameters, and outcomes were compared and analyzed between males and females. In the present study, we analyzed 168 severe patients with COVID-19, including 86 males and 82 females, and 48 patients (28.6%) were diagnosed as critically ill. Of 86 male patients, 12.8% (11/86) died and 75.6% (65/86) were discharged; of 82 female patients, 7.3% (6/82) died and 86.6% (71/82) were discharged. Eleven laboratory parameters showed significant differences between male and female patients, and six of them were higher during the whole clinical course in patients who died than in patients who were discharged. In adjusted logistic regression analysis, males with comorbidities presented a higher risk of being critically ill than males without comorbidities (OR = 3.824, 95% CI = 1.279–11.435). However, this association attenuated to null in female patients (OR = 2.992, 95% CI = 0.937–9.558). A similar sex-specific trend was observed in the relation between age and critically ill conditions. We highlighted sex-specific differences in clinical characteristics and prognosis. Male patients appeared to be more susceptible to age and comorbidities. Sex is an important biological variable that should be considered in the prevention and treatment of COVID-19.

positive: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. METHODS: An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. RESULTS: Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31×10(9)/L; 95% CI, from -35 to -29×10(9)/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48×10(9)/L; 95% CI, -57 to -39×10(9)/L. In the four studies (n=1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). CONCLUSIONS: Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.

positive: Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; a simulation study. Aim To estimate the number of confirmed cases and the rate of death and also to investigate the cause of death in Italy, Iran and South Korea in the next month. Background Growing number of confirmed and deaths cases from the coronavirus worldwide, particularly in Italy, Iran and South Korea, has resulted concerns about the future of these countries and their deterioration. Also the European region is likely to face more casualties due to the delay in the virus reaching most of its regions and, of course, as the trend continues. Methods We conducted a simulation in both current and ideal situation for the next month to predict the death rate and examine the reason for the difference in Italy, Iran and South Korea individually. If we assume the cultural and political factors and age pyramids distribution are similar across regions, the differences are mainly due either to the heavier health-care burden owing to the larger population or to the medical facilities diversities. Results Our results for Italy showed higher death number, but the rate would be more for Iran. South Korea is also expected to have a smaller increase in the number of confirmed cases and deaths compared to Iran and Italy by the next month. Conclusion Given the prevailing conditions around the world and the increasing number of casualties, it is essential that all countries, especially those with fewer days of involvement, shall do their best to avoid major losses and damages.

positive: 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.

positive: The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality Abstract Since December 2019, a viral pneumonia (COVID-19) from Wuhan, China has swept the world. Although the case fatality rate is not high, the number of people infected is large, and there are still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is also an important cause of death. Therefore, the treatment of cytokine storm has become an important part of rescuing severe patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome (CRS). If it can block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe patients. Tocilizumab is a blocker of IL-6R, which can effectively block IL-6 signal transduction pathway. So, tocilizumab is likely to become an effective drug for patients with severe COVID-19.

positive: The host’s angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections

positive: Risk Factors for COVID-19 versus non-COVID-19 related in-hospital and community deaths by Local Authority District in Great Britain Objectives: To undertake a preliminary hypothesis-generating analysis exploring putative risk factors for coronavirus diseae 2019 (COVID-19) population-adjusted deaths, compared with non-COVID-19 related deaths, at a local authority district (LAD) level in hospital, care homes and at home. Design: Ecological retrospective cohort study Setting Local authority districts (LADs) in England, Scotland and Wales (Great Britain (GB)). Participants All LAD deaths registered by week 16 of 2020. Main Outcome Measures Death registration where COVID-19 is mentioned as a contributing factor per 100,000 people in all settings, and in i) cares homes, ii) hospitals or iii) home only, in comparison to non-COVID-19 related deaths. Results Across GB by week 16 of 2020, 20,684 deaths had been registered mentioning COVID-19, equivalent to 25.6 per 100,000 people. Significant risk factors for LAD COVID-19 death in comparison to non-COVID-19 related death were air pollution and proportion of the population who were female. Significant protective factors were higher air temperature and proportion of the population who were ex-smokers. Conversely, for all COVID-19 unrelated deaths in comparison to COVID-19 deaths, higher rates of communal living, higher population rates of chronic kidney disease, chronic obstructive pulmonary disease, cerebrovascular disease deaths under 75 and dementia were predictive of death, whereas, higher rates of flight passengers was protective. Looking at individual setttings, the most notable findings in care homes was Scotland being a significant risk factor for COVID-19 related deaths compared to England. For hospital setting, the proportion of the population who were from black and Asian minority ethnic (BAME) groups significantly predicted COVID-19 related death. Conclusions This is the first study within GB to assess COVID-19 related deaths in comparison to COVID-19 unrelated deaths across hospital, care homes and home combined. As an ecological study, the results cannot be directly extrapolated to individuals. However, the analysis may be informative for public health policy and protective measures. From our hypothesis-generating analysis, we propose that air pollution is a significant risk factor and high temperature a significant protective factor for COVID-19 related deaths. These factors cannot readily be modelled at an individual level. Scottish local authorities and local authorities with a higher proportion of individuals of BAME origin are potential risk factors for COVID-19 related deaths in care homes and in hospitals, respectively. Altogether, this analysis shows the benefits of access to high quality open data for public information, public health policy and further research.

positive: On the molecular determinants the SARS-CoV-2 attack

positive: Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. METHODS: Autopsies were performed on ten African American decedents aged 44-78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. FINDINGS: Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. INTERPRETATION: We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. FUNDING: None.

positive: Clinical features of deaths in the novel coronavirus epidemic in China In response to the recent novel coronavirus outbreak originating in Wuhan, Hubei province, China, observations concerning novel coronavirus mortality are of urgent public health importance. The present work presents the first review of the fatal novel coronavirus cases in China. Clinical data of fatal cases published by the Chinese Government were studied. As of 2 February 2020, the clinical data of 46 fatal cases were identified. The case fatality rate was significantly higher in Hubei province than the rest of China. While 67% of all deceased patients were male, gender was unlikely to be associated with mortality. Diabetes was likely to be associated with mortality. There is, however, not yet sufficient evidence to support the association between hypertension and mortality as similar prevalence of hypertension was also observed in the Hubei population.

positive: Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ2 test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.

positive: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None.

positive: Association between comorbidities and the risk of death in patients with COVID-19: sex-specific differences Background: The coronavirus disease 2019 (Covid-19) spreads rapidly around the world. Objective: To evaluate the association between comorbidities and the risk of death in patients with COVID-19, and to further explore potential sex-specific differences. Methods: We analyzed the data from 18,465 laboratory-confirmed cases that completed an epidemiological investigation in Hubei Province as of February 27, 2020. Information on death was obtained from the Infectious Disease Information System. The Cox proportional hazards model was used to estimate the association between comorbidities and the risk of death in patients with COVID-19. Results: The median age for COVID-19 patients was 50.5 years. 8828(47.81%) patients were females. Severe cases accounted for 20.11% of the study population. As of March 7, 2020, a total of 919 cases deceased from COVID-19 for a fatality rate of 4.98%. Hypertension (13.87%), diabetes (5.53%), and cardiovascular and cerebrovascular diseases CBVDs (4.45%) were the most prevalent comorbidities, and 27.37% of patients with COVID-19 reported having at least one comorbidity. After adjustment for age, gender, address, and clinical severity, patients with hypertension (HR 1.55, 95%CI 1.35-1.78), diabetes (HR 1.35, 95%CI 1.13-1.62), CBVDs (HR 1.70, 95%CI 1.43-2.02), chronic kidney diseases (HR 2.09, 95%CI 1.47-2.98), and at least two comorbidities (HR 1.84, 95%CI 1.55-2.18) had significant increased risks of death. And the association between diabetes and the risk of death from COVID-19 was prominent in women (HR 1.69, 95%CI 1.27-2.25) than in men (HR 1.16, 95%CI 0.91-1.46) (P for interaction = 0.036). Conclusion: Among laboratory-confirmed cases of COVID-19 in Hubei province, China, patients with hypertension, diabetes, CBVDs, chronic kidney diseases were significantly associated with increased risk of death. The association between diabetes and the risk of death tended to be stronger in women than in men. Clinicians should increase their awareness of the increased risk of death in COVID-19 patients with comorbidities.

positive: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO(2)/FiO(2)≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.

positive: Dynamic profile of severe or critical COVID-19 cases In December 2019, a cluster of acute respiratory illness, now known as SARS-CoV-2 pneumonia, occurred in Wuhan, China. World Health Organization (WHO) declared the rapidly spreading coronavirus outbreak a pandemic on March 11, 2020, acknowledging what has seemed clear for some time-the virus will likely spread to all countries on the globe. As of February 11, 2020, the Chinese Center for Disease Control and Prevention (China CDC) has officially reported that there are 2.0% (889) asymptomatic cases, 2.3% (1,023) death cases, and 80.9% mild cases among 44,672 confirmed cases. 51.4% (22,981) were male and 48.6% (21,691) were female. Lymphopenia, in particular T lymphopenia, was common among patients with SARS-COV-2 in the observation. A notable drop in CD4 and CD8 lymphocyte counts occurred early in the course of the syndrome and was associated with adverse outcomes. The appearing a phenomenon of lymphocyte depletion (PLD) suggested severe adverse outcomes. The outcome observed: 60% had discharged and 20% had die.

positive: Early postmortem brain MRI findings in COVID-19 non-survivors Importance: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuro-invasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) data in COVID-19 patients are scarce due to difficulties to obtain such examination in infected unstable patients during the COVID-19 outbreak. Objective: To investigate the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. Design: Prospective, case series study with postmortem brain MRI obtained early (<24h) after death. Setting: Monocentric study. Participants: From 31/03/2020 to 24/04/2020, consecutive decedents who fulfilled the following inclusion criteria were included: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest computerized tomographic (CT) scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. Main Outcome(s) and Measure(s): Signs of acute brain injury and MRI signal abnormalities along the olfactory tract and brainstem were searched independently by 3 neuroradiologists, then reviewed with neurologists and clinicians. Results: Among the 62 patients who died from COVID-19 during the inclusion period, 19 decedents fulfilled inclusion criteria. Subcortical micro- and macro-bleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES, one decedent), and nonspecific deep white matter changes (one decedent) were observed. Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality. Conclusions and Relevance: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19 that might be triggered by the virus-induced endothelial disturbances. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. The absence of brainstem MRI abnormalities does not support a brain-related contribution to respiratory distress in COVID-19.

positive: 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.

positive: Association between epidemic dynamics of Covid-19 infection and ABO blood group types Background: Covid-19 pandemic is the most critical challenge nowadays for the manhood, and the infection and death cases are still speedily increasing. Since there are no available vaccine and specifically effective treatment, to break the infectious way of the pandemic remains the unique measure to efficiently combat Covid-19 infection. Understanding factors that affect the Covid-19 infection can help make better balance between activity restriction and infection dynamics. This study sought to investigate association between Covid-19 infection and blood type distribution. Methods: The big data provided by World Health Organization and Johns Hopkins University were taken to assess epidemic dynamics of Covid-19 infection. Growth rate and doubling time of infection and death cases, reproductive number, infection and death cases in the mid-exponential phase were analyzed in relation to blood type distribution. Results: Growth rate of infection and death cases correlated significantly to blood type A proportion of the population positively while to blood type B proportion negatively. In comparison with lower blood type A population (< 30%) people with higher blood type A ([≥] 30%) had more infection and death cases in the early exponential phase, higher growth rates, and shorter case doubling time for infection and death. Discussion: Covid-19 infection is significantly associated with blood type distribution and people with blood type A are more susceptible to Covid-19 infection and have higher epidemic dynamics and higher case fatality rate. The results of this study provide important and useful information for fighting Covid-19 pandemic.

positive: Coronavirus Disease 2019 in the Perioperative Period of Lung Resection: A Brief Report From a Single Thoracic Surgery Department in Wuhan, People’s Republic of China Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, People’s Republic of China, and has subsequently spread worldwide. Clinical information on patients who contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the perioperative period is limited. Here, we report seven cases with confirmed SARS-CoV-2 infection in the perioperative period of lung resection. Retrospective analysis suggested that one patient had been infected with the SARS-CoV-2 infection before the surgery and the other six patients contracted the infection after the lung resection. Fever, lymphopenia, and ground-glass opacities revealed on computed tomography are the most common clinical manifestations of the patients who contracted COVID-19 after the lung resection. Pathologic studies of the specimens of these seven patients were performed. Pathologic examination of patient 1, who was infected with the SARS-CoV-2 infection before the surgery, revealed that apart from the tumor, there was a wide range of interstitial inflammation with plasma cell and macrophage infiltration. High density of macrophages and foam cells in the alveolar cavities, but no obvious proliferation of pneumocyte, was found. Three of seven patients died from COVID-19 pneumonia, suggesting lung resection surgery might be a risk factor for death in patients with COVID-19 in the perioperative period.

positive: Mortality and survival of COVID-19 This study aims to identify the risk factors associated with mortality and survival of COVID-19 cases in a state of the Brazilian Northeast. It is a historical cohort with a secondary database of 2070 people that presented flu-like symptoms, sought health assistance in the state and tested positive to COVID-19 until 14 April 2020, only moderate and severe cases were hospitalised. The main outcome was death as a binary variable (yes/no). It also investigated the main factors related to mortality and survival of the disease. Time since the beginning of symptoms until death/end of the survey (14 April 2020) was the time variable of this study. Mortality was analysed by robust Poisson regression, and survival by Kaplan–Meier and Cox regression. From the 2070 people that tested positive to COVID-19, 131 (6.3%) died and 1939 (93.7%) survived, the overall survival probability was 87.7% from the 24th day of infection. Mortality was enhanced by the variables: elderly (HR 3.6; 95% CI 2.3–5.8; P < 0.001), neurological diseases (HR 3.9; 95% CI 1.9–7.8; P < 0.001), pneumopathies (HR 2.6; 95% CI 1.4–4.7; P < 0.001) and cardiovascular diseases (HR 8.9; 95% CI 5.4–14.5; P < 0.001). In conclusion, mortality by COVID-19 in Ceará is similar to countries with a large number of cases of the disease, although deaths occur later. Elderly people and comorbidities presented a greater risk of death.

positive: Early estimation of the risk factors for hospitalisation and mortality by COVID-19 in Mexico Background. With its high prevalence of chronic non-degenerative diseases, it is suspected that in Mexico there is a high risk of fatal complications from COVID-19. The present study aims to estimate the risk factors for hospitalisation and death in the Mexican population infected by SARS-CoV-2. Methods and Findings. We used the publicly available data released by the Epidemiological Surveillance System for Viral Respiratory Diseases of the Mexican Ministry of Health (Secretaria de Salud, SS). All records of positive SARS-CoV-2 cases were included. Two multiple logistic regression models were fitted to estimate the association between the hospitalisation and mortality, with other covariables. Data on 10,544 individuals (57.68% men), with mean age 46.47 SD 15.62, were analysed. Men were about 1.54 times as likely to be hospitalized than women (p<0.001, 95% C.I. 1.37-1.74); individuals aged 50-74 and >=74 years were more likely to be hospitalized than people from 25-49 years (OR 2.05, p<0.001, 95% C.I. 1.81-2.32, and OR 23.84, p<0.001, 95% C.I. 2.90-5.15, respectively). People with hypertension, obesity, and diabetes were more likely to be hospitalised than people without these morbidities (p<0.01). Men had more risk of death in comparison to women (OR=1.53, p<0.001, 95% C.I. 1.30-1.81) and individuals aged 50-74 and [≥]75 years were more likely to die than people from 25-49 years (OR 1.96, p<0.001, 95% C.I. 1.63-2.34, and OR 3.74, p<0.001, 95% C.I. 2.80-4.98, respectively). Hypertension, obesity, and diabetes presented in combination, provided a higher risk of dying in comparison to not having these diseases (OR=2.10; p<0.001, 95% C.I. 1.50-2.93). Hospitalisation, intubation and pneumonia conferred a higher risk of dying (OR 5.02, p<0.001, 95% C.I. 3.88-6.50; OR 4.27, p<0.001, 95% C.I. 3.26-5.59, and OR=2.57; p<0.001, 95% C.I. 2.11-3.13, respectively). The main limitation of our study is the lack of information on mild (asymptomatic) or moderate cases of COVID-19. Conclusions. The present study points out that in Mexico, where an important proportion of the population develops two or more chronic conditions simultaneously, high mortality is a sever outcome for those infected by SARS-CoV-2.

positive: 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.

positive: Considerations for people with diabetes during the Coronavirus Disease (COVID-19) Pandemic Abstract Introduction The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of SARS-CoV-2 on people with diabetes. Aims (1) To characterise the outcomes of SARS-CoV-2 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management. Methods A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV in the context of diabetes. Conclusion People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.

positive: Real-time estimation and prediction of mortality caused by COVID-19 with patient information based algorithm Abstract The global COVID-19 outbreak is worrisome both for its high rate of spread, and the high case fatality rate reported by early studies and now in Italy. We report a new methodology, the Patient Information Based Algorithm (PIBA), for estimating the death rate of a disease in real-time using publicly available data collected during an outbreak. PIBA estimated the death rate based on data of the patients in Wuhan and then in other cities throughout China. The estimated days from hospital admission to death was 13 (standard deviation (SD), 6 days). The death rates based on PIBA were used to predict the daily numbers of deaths since the week of February 25, 2020, in China overall, Hubei province, Wuhan city, and the rest of the country except Hubei province. The death rate of COVID-19 ranges from 0.75% to 3% and may decrease in the future. The results showed that the real death numbers had fallen into the predicted ranges. In addition, using the preliminary data from China, the PIBA method was successfully used to estimate the death rate and predict the death numbers of the Korean population. In conclusion, PIBA can be used to efficiently estimate the death rate of a new infectious disease in real-time and to predict future deaths. The spread of 2019-nCoV and its case fatality rate may vary in regions with different climates and temperatures from Hubei and Wuhan. PIBA model can be built based on known information of early patients in different countries.

positive: COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study BACKGROUND: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. METHODS: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. FINDINGS: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56–10·02]; p<0·0001), being male (1·67 [1·19–2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36–2·80]; p<0·001) and cardiovascular disease (2·32 [1·47–3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81–1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. INTERPRETATION: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. FUNDING: University of Birmingham, University of Oxford.

positive: Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. METHODS: Autopsies were performed on ten African American decedents aged 44–78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. FINDINGS: Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. INTERPRETATION: We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. FUNDING: None.

positive: On the Alert for Cytokine Storm: Immunopathology in COVID‐19 Poor outcomes in COVID‐19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID‐19.

positive: Obesity - a risk factor for increased COVID-19 prevalence, severity and lethality Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible. The global spread of COVID-19 can be described as the worst pandemic in humanity in the last century. To date, COVID-19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID-19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID-19 will affect its prognosis. Finally, pregnancy-associated obesity needs to be studied further in connection to COVID-19 as this infection could pose high risk both to pregnant women and the fetus.

positive: Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy BACKGROUND: aim of the present study is to describe characteristics of COVID-19 related deaths and to compare the clinical phenotype and course of COVID-19 related deaths occurring in adults (< 65 years) and older adults (≥ 65 years). METHODS: medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥ 65 years) were revised to extract information on demographics, pre-existing comorbidities, and in-hospital complications leading to death. RESULTS: Older adults (≥ 65 years) presented with a higher number of comorbidities compared to those aged < 65 years (3.3 ± 1.9 vs. 2.5 ± 1.8, p<0.001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (≥ 65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (< 65 years); 10.9% of younger patients (< 65 years) had no comorbidities, compared to 3.2% of older patients (≥ 65 years). The younger adults had a higher rate of non-respiratory complications than older patients including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%) and superinfections (30.9% vs. 9.8%). CONCLUSIONS: individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occurs in healthy adults with no pre-existing conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.

positive: 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.

positive: Association Between Hypoxemia and Mortality in Patients With COVID-19 OBJECTIVE: To identify markers associated with in-hospital death in patients with coronavirus disease 2019 (COVID-19)-associated pneumonia. PATIENTS AND METHODS: A retrospective cohort study was conducted of 140 patients with moderate to critical COVID-19-associated pneumonia requiring oxygen supplementation admitted to the hospital from January 28, 2020, through February 28, 2020, and followed up through March 13, 2020, in Union Hospital, Wuhan, China. Oxygen saturation (SpO2) and other measures were tested as predictors of in-hospital mortality in survival analysis. RESULTS: Of 140 patients with COVID-19-associated pneumonia, 72 (51.4%) were men, with a median age of 60 years. Patients with SpO2 values of 90% or less were older and were more likely to be men, to have hypertension, and to present with dyspnea than those with SpO2 values greater than 90%. Overall, 36 patients (25.7%) died during hospitalization after median 14-day follow-up. Higher SpO2 levels after oxygen supplementation were associated with reduced mortality independently of age and sex (hazard ratio per 1-U SpO2, 0.93; 95% CI, 0.91 to 0.95; P<.001). The SpO2 cutoff value of 90.5% yielded 84.6% sensitivity and 97.2% specificity for prediction of survival. Dyspnea was also independently associated with death in multivariable analysis (hazard ratio, 2.60; 95% CI, 1.24 to 5.43; P=.01). CONCLUSION: In this cohort of patients with COVID-19, hypoxemia was independently associated with in-hospital mortality. These results may help guide the clinical management of patients with severe COVID-19, particularly in settings requiring strategic allocation of limited critical care resources. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2000030852.

positive: 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.

positive: Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of Valcamonica, Italy. Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.

positive: Re-analysis of SARS-CoV-2 infected host cell proteomics time-course data by impact pathway analysis and network analysis. A potential link with inflammatory response The disease known as coronavirus disease 19 (COVID-19), potentially caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has hit the world hard, and has led to an unprecedent health and economic crisis. In order to develop treatment options able to stop or ameliorate SARS-CoV-2 effects, we need to understand the biology of the virus inside cells, but this kind of studies are still scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. In the present study, we use the publicly available proteomics data from this study to re-analyze the mechanisms altered by the virus infection by impact pathways analysis and network analysis. Proteins linked to inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be regulated. The up-regulation of the inflammatory-related proteins observed could be linked to the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients.

positive: Rapid Progression to Acute Respiratory Distress Syndrome: Review of Current Understanding of Critical Illness from COVID-19 Infection The coronavirus disease 2019 (COVID-19) outbreak that started in Wuhan, Hubei province, China in December 2019 has now extended across the globe with >100,000 cases and 3,000 deaths reported in 93 countries as of 7 March 2020 We report a case of COVID-19 infection in a 64-year-old man who developed rapidly worsening respiratory failure and acute respiratory distress syndrome (ARDS) that required intubation As the clinical spectrum of COVID-19 ranges widely from mild illness to ARDS with a high risk of mortality, there is a need for more research to identify early markers of disease severity Current evidence suggests that patients with advanced age, pre-existing comorbidities or dyspnoea should be closely monitored, especially at 1-2 weeks after symptom onset It remains to be seen if laboratory findings such as lymphopenia or elevated lactate dehydrogenase may serve as early surrogates for critical illness or markers of disease recovery Management of ARDS in COVID-19 remains supportive while we await results of drug trials More studies are needed to understand the incidence and outcomes of ARDS and critical illness from COVID-19, which will be important for critical care management and resource planning

positive: Clinical and Transmission Characteristics of Covid-19 — A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential “super spreader” may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.

positive: Spatial variability in the risk of death from COVID-19 in Italy, 2020 Objectives: Italy is bearing the brunt of the COVID-19 pandemic, as the death toll there has already surpassed that in Wuhan, the city in China where the coronavirus emerged in December 2019. Here we employ statistical methods to assess the severity of COVID-19 pandemic across different regions of Italy. Method: We manually retrieved the daily cumulative numbers of laboratory-confirmed cases and deaths attributed to COVID-19 stratified by region in Italy. We estimated both the crude and time-delay adjusted case fatality ratio across five geographic regions of Italy. Results: The Northwest that includes Lombardy exhibited the highest time-delay-adjusted CFR at 23.0% followed by the Northeast (14.2%), the Center region (11.6%) and the South region (12.1%). The Island region has exhibited the lowest CFR (9.6%). Conclusion: Our estimates in the Northwest and the Northeast are higher than those reported from most affected areas in China. The CFR in Northwest Italy is 1.9-fold higher than that in Wuhan. Our finding reflects the need of urgent medical support in the Northwest region and the appropriate planning and supplies procurement in other regions of Italy focusing on medical care delivery to those who are at the highest risk of poorer outcomes due to COVID-19.

positive: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

positive: Cognitive impairment is a common comorbidity in COVID-19 deceased patients. A hospital-based retrospective cohort study. Introduction: Little is known about the relation of cognitive impairment (CI) to COVID-19 mortality. Here, we analyse the frequency of CI in deceased COVID-19 patients. Methods: We included 477 adult cases that died after admission from March 1 to March 31, 2020: 281 with confirmed COVID-19, 58 probable COVID-19, and 138 who died of other causes. Results: The number of comorbidities was high in the confirmed COVID-19, and CI was common (30%: 21.1% dementia; 8.9% mild cognitive impairment). Subjects with CI were older, more lived in nursing homes and had shorter times from symptom onset to death than those without CI. COVID-19 patients with CI were rarely admitted to the ICU and fewer received non-invasive mechanical ventilation, but palliative care was provided more often. Conclusions: Dementia is a frequent comorbidity in COVID-19 deceased patients. The burden of COVID-19 in the dementia community will be high.

positive: 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.

positive: Retrospective Analysis of 61 Cases of Children Died of Viral Pneumonia. Abstract Objective To retrospectively analyze the forensic and pathological postmortem examination and clinical data of children who died of viral pneumonia in identification of cause of death cases and to discuss the clinical characteristics and pathological features of viral pneumonia in children, in order to provide reference to pathological diagnosis of viral pneumonia in children caused by severe acute respiratory syndrome coronavirus-2 （SARS-CoV-2） infection. Methods In this study, postmortem examination data from the institute of 61 cases of children whose cause of death were identified as viral pneumonia in recent years were collected. The gender, age, clinical symptoms and pathological features were comparatively analyzed. Results Among the 61 cases of children who died of viral pneumonia, most were within 2 years old （83.61%）, and a large proportion died within 2 weeks after the onset of the disease （91.80%）. General changes in postmortem examination included respiratory mucosal hyperemia, pleural effusion, pulmonary swelling, variegated pulmonary pleura and serosa, focal hemorrhage and edema of the cut surface of the lung. A large proportion of children had enlarged mesenteric lymph nodes （83.61%）, and 21.31% of children had thymic dysplasia. Histopathological changes included pulmonary alveoli and interstitial edema, pulmonary hemorrhage, alveolar epithelial shedding, serous and （or） fibrous exudation in the alveoli, formation of viral inclusions, formation of transparent membranes, infiltration of inflammatory cells that mainly consisted of macrophages and lymphocytes in interstitial substance and alveoli. Viral infections often affected the heart and gastrointestinal tract. Conclusion The clinical symptoms of children with viral pneumonia are difficult to notice, and because their immune system is not fully developed and they have poor autoimmunity, they can easily get into a critical condition and even die. Through analysis of the characteristics of forensic autopsy and histopathological changes, this study could provide reference for pathological diagnosis of viral pneumonia.

positive: Clinical characteristics and outcomes of cancer patients with COVID-19. OBJECTIVE This retrospective study aimed to analysis clinical characteristics and outcomes of cancer patients with novel coronavirus disease-19 (COVID-19). METHOD Medical records, laboratory results and radiologic findings of 52 cancer patients with COVID-19 were collected, clinical characteristics and outcomes were summarized. RESULTS A total of 52 cancer patients with COVID-19 were included. Median age of 52 cancer patients with COVID-19 was 63 years (34-98). 33(63.5%) patients were mild and 19(36.5%) were severe/critical. Lung cancer was the most frequent cancer type (10, 19.2%). The common symptoms were as follows: fever (25%), dry cough (17.3%), chest distress (11.5%) and fatigue (9.6%).There were 33(63.5%) patients had comorbidities, the most common symptom was hypertension (17, 51.5%). 26(78.8%) patients developed pneumonia on admission. Lymphocytes (0.6×109 /L) decreased in both mild and severe/critical patients. Median levels of D-dimer, C-reactive protein(CRP), procalcitonin (PCT) and lactate dehydrogenase(LDH) were 2.8 mg/L, 70.5 mg/L, 0.3 ng/mL, and 318 U/L respectively, which increased significantly in severe/critical patients compared to the mild patients. Interleukin 6(IL-6) (12.6 pg/ml) increased in both mild and severe/critical patients, there was a significant difference between them. Complications were observed in 29(55.8%) patients, such as liver injury (19, 36.5%), acute respiratory distress syndrome (ARDS) (9, 17.3%), sepsis (8, 15.4%), myocardial injury (8, 15.4%), renal insufficiency (4, 7.7%), and multiple organ dysfunction syndrome (MODS) (3, 5.8%).11(21.2%) cancer patients died. CONCLUSION The infection rate of severe acute respiratory syndrome coronavirus 2(SARS-COV-2) in cancer patients was higher than the general population, cancer patients with COVID-19 showed deteriorating conditions and poor outcomes. This article is protected by copyright. All rights reserved.

positive: Is death from Covid-19 a multistep process? Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.

positive: Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients’ mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

positive: 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.

positive: A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: an observational cohort study. Abstract Background The COVID-19 pandemic continues to escalate. There is urgent need to stratify patients. Understanding risk of deterioration will assist in admission and discharge decisions, and help selection for clinical studies to indicate where risk of therapy-related complications is justified. Methods An observational cohort of patients acutely admitted to two London hospitals with COVID-19 and positive SARS-CoV-2 swab results was assessed. Demographic details, clinical data, comorbidities, blood parameters and chest radiograph severity scores were collected from electronic health records. Endpoints assessed were critical care admission and death. A risk score was developed to predict outcomes. Findings Analyses included 1,157 patients. Older age, male sex, comorbidities, respiratory rate, oxygenation, radiographic severity, higher neutrophils, higher CRP and lower albumin at presentation predicted critical care admission and mortality. Non-white ethnicity predicted critical care admission but not death. Social deprivation was not predictive of outcome. A risk score was developed incorporating twelve characteristics: age>40, male, non-white ethnicity, oxygen saturations<93%, radiological severity score>3, neutrophil count>8.0 x109/L, CRP>40 mg/L, albumin<34 g/L, creatinine>100 µmol/L, diabetes mellitus, hypertension and chronic lung disease. Risk scores of 4 or higher corresponded to a 28-day cumulative incidence of critical care admission or death of 40.7% (95% CI: 37.1 to 44.4), versus 12.4% (95% CI: 8.2 to 16.7) for scores less than 4. Interpretation Our study identified predictors of critical care admission and death in people admitted to hospital with COVID-19. These predictors were incorporated into a risk score that will inform clinical care and stratify patients for clinical trials.

positive: 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.

positive: COVID-19 and diabetes: What does the clinician need to know? COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.

positive: Clinical characteristics and outcomes of patients with severe covid-19 with diabetes OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO2/FiO2≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.

positive: Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.

negative: Predicting the ultimate outcome of the COVID-19 outbreak in Italy During the COVID-19 outbreak, it is essential to monitor the effectiveness of measures taken by governments on the course of the epidemic. Here we show that there is already a sufficient amount of data collected in Italy to predict the outcome of the process. We show that using the proper metric, the data from Hubei Province and Italy has striking similarity, which enables us to calculate the expected number of confirmed cases and the number of deaths by the end of the process. Our predictions will improve as new data points are generated day by day, which can help to make further public decisions. The method is based on the data analysis of logistic growth equations describing the process on the macroscopic level. At the time of writing of the first version, the number of fatalities in Italy was expected to be 6000, and the predicted end of the crisis was April 15, 2020. In this new version, we discuss what changed in the two weeks which passed since then. The trend changed drastically on March 17, 2020, when the Italian health system reached its capacity limit. Without this limit, probably 3500 more people would have died. Instead, due to the limitations, 17.000 people are expected to die now, which is a five-fold increase. The predicted end of the crisis now shifted to May 8, 2020.

negative: An outbreak of COVID‐19 caused by a new coronavirus: what we know so far

negative: Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19 Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12070-020-01863-4) contains supplementary material, which is available to authorized users.

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: The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia OBJECTIVE: The aim of this study was to investigate the clinical and computed tomography (CT) features associated with severe and critical coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Eighty-three patients with COVID-19 pneumonia including 25 severe/critical cases and 58 ordinary cases were enrolled. The chest CT images and clinical data of them were reviewed and compared. The risk factors associated with disease severity were analyzed. RESULTS: Compared with the ordinary patients, the severe/critical patients had older ages, higher incidence of comorbidities, cough, expectoration, chest pain, and dyspnea. The incidences of consolidation, linear opacities, crazy-paving pattern, and bronchial wall thickening in severe/critical patients were significantly higher than those of the ordinary patients. Besides, severe/critical patients showed higher incidences of lymph node enlargement, pericardial effusion, and pleural effusion than the ordinary patients. The CT scores of severe/critical patients were significantly higher than those of the ordinary patients (P < 0.001). Receiver operating characteristic curve showed that the sensitivity and specificity of CT score were 80.0% and 82.8%, respectively, for the discrimination of the 2 types. The clinical factors of age older than 50 years, comorbidities, dyspnea, chest pain, cough, expectoration, decreased lymphocytes, and increased inflammation indicators were risk factors for severe/critical COVID-19 pneumonia. Computed tomography findings of consolidation, linear opacities, crazy-paving pattern, bronchial wall thickening, high CT scores, and extrapulmonary lesions were features of severe/critical COVID-19 pneumonia. CONCLUSIONS: There are significant differences in clinical symptoms, laboratory examinations, and CT manifestations between the ordinary patients and the severe/critical patients. Many factors are related to the severity of the disease, which can help clinicians to judge the severity of the patient and evaluate the prognosis.

negative: An Ounce of Prevention: Coronavirus (COVID-19) and Mass Gatherings Widespread, non-stop, and often sensational coverage of the coronavirus (COVID-19) has caught many governments flat-footed in efforts to protect the health and safety of their citizens. In response to the current global health event, the World Health Organization (WHO) declared COVID-19 a pandemic. Mass gatherings present a historic challenge in protecting the health and safety of attendees. The majority of the prominent mass gatherings are religious in nature. Global sporting events, such as the Olympics and the World Cup, pose unique health risks to attendees and host nations. Deferment or cancellation of such mass gatherings may exert an extraordinary economic loss to the host nation. Universal adoption of best practices for infection control is the surest way for governments to prepare for mass gatherings. In these uncertain times, it is up to intergovernmental organizations to be the voice of reason.

negative: Understanding the emerging coronavirus: what it means for health security and infection prevention

negative: An immunoelectron microscopic and immunofluorescent study on the antigenic relationship between the coronavirus-like agent, CV 777, and several coronaviruses A possible antigenic relationship between the porcine enteropathogenic coronavirus-like agent (CVLA) and 6 known coronaviruses was examined by immunoelectron microscopy (IEM) and by immunofluorescence (IF). CVLA did not show cross reactivity with infectious bronchitis virus, transmissible gastroenteritis virus (TGEV), canine coronavirus (CCV) hemagglutinating encephalomyelitis virus (HEV), neonatal calf diarrhea coronavirus (NCDCV) or feline infectious peritonitis virus (FIPV). Antigenic relationship was detected by IEM between TGEV and CCV, NCDCV and HEV and by IF between TGEV and CCV, TGEV and FIPV, HEV and NCDCV.

negative: Herausforderungen in der Seuchenkontrolle und der jetzigen Pandemie durch verzerrte Verteilungen BACKGROUND: The pandemic phase 3—mitigation—by the SARS-Coronavirus‑2 is currently taking on speed in Germany. Skewed distributions of key epidemiological parameters of the virus and patient care are a challenge for the control of the outbreak as well as keeping the system functional. METHODS: The skewed parameters—pre-patency period, incubation period, duration of viral shedding and time to admission to hospital—are analyzed in regard to their impact and possible countermeasures. RESULTS: The skewed distributions are exclusively time related variables. They are a handicap for outbreak control as well patient management. Optimization between residual open flanks and the efforts to close them is difficult. The main stakeholders are the local health departments, the diagnostic laboratories, the health care infrastructure and finally the citizens in regard to the burden due to non-pharmaceutical interventions including quarantine and isolation. The duration of quarantine and isolation should urgently be shortened for health care workers (HCW) as well as people in critical infrastructure by ready (re-) testing. Calculated risks have to be taken within a phase 3 of a pandemic to keep a system going. CONCLUSIONS: The skewed distributions are a special challenge for infectious disease control. In the case of ending quarantine and isolation in phase 3 of the pandemic, they should be judged specifically in regard to the client/patient. Cumulative distribution functions are very helpful in this regard.

negative: Dysregulation of immune response in patients with COVID-19 in Wuhan, China BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.

negative: Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update As the time for finding a definitive and safe cure as a vaccine for novel Corona Virus Disease 2019 (Covid-19) is still far, there is need to study in depth about the other potential drugs, which can save millions of lives due to Covid-19 pandemic. Right at the center of the debate is the use of drug “Hydroxychloroquine” as a prophylaxis as well as a treatment strategy against Covid-19 in conjunction with azithromycin. In this review, we will study the cellular and molecular aspects of hydroxychloroquine, which had driven its use in Covid-19 patients, as well as its chemistry and pharmacokinetics along with clinical trials going on worldwide using hydroxychloroquine against Covid-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12291-020-00900-x) contains supplementary material, which is available to authorized users.

negative: Surgical Strategy During the COVID-19 Pandemic in a University Metropolitan Hospital in Milan, Italy The COVID-19 pandemic has spread rapidly, forcing some drastic changes not only in our daily lives, but also in our clinical and surgical activities. Given our extensive Italian experience, we hereby describe how our surgical unit activity has changed and how, in some cases, it was necessary to modify surgical strategies. We hope our experience can be shared with our global colleagues who are suffering under similar condition.

negative: Supporting families in end-of-life care and bereavement in the COVID-19 era

negative: COVID-SGIS: A smart tool for dynamic monitoring and temporal forecasting of Covid-19 Objective The new kind of coronavirus SARS-Cov2 spread to countries in all continents in the World. The coronavirus disease 2019 (Covid-19) causes fever, cough, sore throat, and in severe cases shortness of breath and death. To evaluate strategies, it is necessary to forecast the number of cases and deaths, in order to aid the stakeholders in the process of making decisions against the disease. We propose a system for real-time forecast of the cumulative cases of Covid-19 in Brazil. Study Design Monitoring of all Brazilian cities using oficial information from the National Notification System, from March to May 2020, concentrated on Brazil.io databases. Training and evaluation of ARIMA and other machine learning algorithms for temporal forecasting using correlation indexes (Pearson's, Spearman's, and Kendall's) and RMSE(%). Validation from the relative errors of the following six days. Methods Our developed software, COVID-SGIS, captures information from the 26 states and the Distrito Federal at the Brazil.io database. From these data, ARIMA models are created for the accumulation of confirmed cases and death cases by Covid-19. Finally, six-day forecasts graphs are available for Brazil and for each of its federative units, separately, with a 95% CI. In addition to these predictions, the worst and best scenarios are also presented. Results ARIMA models were generated for Brazil and its 27 federative units. The states of Bahia, Maranhao, Piaui, Rio Grande do Norte, Amapa, Rondonia every day of the predictions were in the projection interval. The same happened to the states of Espirito Santo, Minas Gerais, Parana and Santa Catarina. In Brazil, the percentage error between the predicted values and the actual values varied between 2.56% and 6.50%. For the days when the forecasts outside the prediction interval, the percentage errors in relation to the worst case scenario were below 5%. The states of Bahia, Maranhao, Piaui, Rio Grande do Norte, Amapa, and Rondonia every day of the predictions were in the projection interval. The same happened to the states of Espirito Santo, Minas Gerais, Parana and Santa Catarina. Conclusion The proposed method for dynamic forecasting may be used to guide social policies and plan direct interventions in a robust, flexible and fast way. Since it is based on information from multiple databases, it can be adapted to the different realities, becoming an important tool to guide the course of politics and action against Covid-19 pandemic worldwide.

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: Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic Abstract Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic.

negative: Genetic diversity and evolution of SARS-CoV-2 Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.

negative: Analysis of the mechanism by which BALB/c mice having prior immunization with nucleocapsid protein of SARS-CoV develop severe pneumonia after SARS-CoV infection Abstract The precise mechanism of severe acute respiratory syndrome (SARS), which is caused by SARS-associated coronavirus (SARS-CoV), is still unclear. We generated recombinant vaccinia virus (rVV) LC16m8 strain which simultaneously expresses four structural proteins of SARS-CoV, including nucleocapsid (N), membrane (M), envelop (E), spike (S) proteins (rVV-NMES) and reported that old BALB/c mice having prior immunization with rVV-NMES develop severe pneumonia similar to those of control mice though rVV-NMES-immunized mice showed lower pulmonary viral titer than in the control mice. Furthermore, we determined which SARS-CoV structural protein for the prior rVV-immunization is responsible for the severe pneumonia after the SARS-CoV infection as observed in the rVV-NMES-immunized mice. Old BALB/c mice were inoculated intradermally with rVV that expressed each structural proteins of SARS-CoV (rVV-N, -M, -E, or -S) with or without rVV-S and then infected intranasally with SARS-CoV more than 4 weeks later. At 9 days after SARS-CoV infection, the rVV-N-immunized mice show more severe pneumonia than in other groups. Furthermore, significant up-regulation of Th1 (IL-2)- and Th2 (IL-4 and IL-5)-bias cytokines and down-regulation of anti-inflammatory cytokine (IL-10 and TGF-β) were observed in rVV-N-immunized mice, resulting in the intensive infiltration of immunocompetent cells into the lung. In contrast, rVV-S-immunized mice showed only low pulmonary viral tier and slight pneumonia. However, the mice having co-immunization with both rVV-N and rVV-S showed severe pneumonia though their pulmonary viral titer was low. These results suggest that an excessive host immune response against the N protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.

negative: To All Doctors: What You Can Do to Help as a Bunch of Older People Are About to Get Sick and Die

negative: A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.

negative: All-Cause Mortality in Tianjin, China, 1999-2004 INTRODUCTION: We analyzed trends of major causes of death in Tianjin, China, from 1999 through 2004 to better inform disease prevention and control programs and policies. METHODS: To report all-cause deaths among Tianjin residents from 1999 through 2004, we standardized mortality rates to the world population in 2000. We analyzed age, sex, and geographic distribution of deaths from different causes and the leading causes of death in Tianjin. RESULTS: The 5 leading causes of death in Tianjin were cardiovascular disease, cerebrovascular disease, malignant neoplasm, chronic lower respiratory disease, and injuries and poisoning. Mortality in Tianjin declined from 0.60% in 1999 to 0.48% in 2004. Noncommunicable diseases accounted for more than 80% of all deaths. Infant and maternal mortality in Tianjin were low. Life expectancy of Tianjin residents increased every year but was consistently longer in women. When deaths from the main chronic diseases are not considered, life expectancy lengthens substantially. CONCLUSION: Chronic diseases are the leading cause of death in Tianjin, China. China should commit additional resources to supporting chronic disease prevention and control programs, including proven special health promotion projects.

negative: Article 14 Prevention of Spread of Disease Each contracting State agrees to take effective measures to prevent the spread by means of air navigation of cholera, typhus (epidemic), smallpox, yellow fever, plague, and such other communicable diseases as the contracting States shall from time to time decide to designate, and to that end contracting States will keep in close consultation with the agencies concerned with international regulations relating to sanitary measures applicable to aircraft. Such consultation shall be without prejudice to the application of any existing international convention on this subject to which the contracting States may be parties.

negative: Determinants of health literacy and health behavior regarding infectious respiratory diseases: a pathway model BACKGROUND: Health literacy has been defined as the degree to which individuals have the capacity to obtain, process, and understand the basic health information and services needed to make appropriate health decisions. Currently, few studies have validated the causal pathways of determinants of health literacy through the use of statistical modeling. The purpose of the present study was to develop and validate a health literacy model at an individual level that could best explain the determinants of health literacy and the associations between health literacy and health behaviors even health status. METHODS: Skill-based health literacy test and a self-administrated questionnaire survey were conducted among 3222 Chinese adult residents. Path analysis was applied to validate the model. RESULTS: The model explained 38.6% of variance for health literacy, 11.7% for health behavior and 2.3% for health status: (GFI = 0.9990; RMR = 0.0521; χ(2) = 10.2151, P = 0.1159). Education has positive and direct effect on prior knowledge (β = 0.324) and health literacy (β = 0.346). Health literacy is also affected by prior knowledge (β = 0.245) and age (β = -0.361). Health literacy is a direct influencing factor of health behavior (β = 0.101). The most important factor of health status is age (β = 0.107). Health behavior and health status have a positive interaction effect. CONCLUSION: This model explains the determinants of health literacy and the associations between health literacy and health behaviors well. It could be applied to develop intervention strategies to increase individual health literacy, and then to promote health behavior and health status.

negative: Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3′-digallate (TF3) SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS). The virally encoded 3C-like protease (3CL(Pro)) has been presumed critical for the viral replication of SARS-CoV in infected host cells. In this study, we screened a natural product library consisting of 720 compounds for inhibitory activity against 3CL(Pro). Two compounds in the library were found to be inhibitive: tannic acid (IC(50) = 3 µM) and 3-isotheaflavin-3-gallate (TF2B) (IC(50) = 7 µM). These two compounds belong to a group of natural polyphenols found in tea. We further investigated the 3CL(Pro)-inhibitory activity of extracts from several different types of teas, including green tea, oolong tea, Puer tea and black tea. Our results indicated that extracts from Puer and black tea were more potent than that from green or oolong teas in their inhibitory activities against 3CL(Pro). Several other known compositions in teas were also evaluated for their activities in inhibiting 3CL(Pro). We found that caffeine, (—)-epigallocatechin gallte (EGCg), epicatechin (EC), theophylline (TP), catechin (C), epicatechin gallate (ECg) and epigallocatechin (EGC) did not inhibit 3CL(Pro) activity. Only theaflavin-3,3′-digallate (TF3) was found to be a 3CL(Pro) inhibitor. This study has resulted in the identification of new compounds that are effective 3CL(Pro) inhibitors.

negative: Prudently conduct the engineering and synthesis of the SARS-CoV-2 virus Abstract Regarding to the recent work of engineering SARS-CoV-19 virus and the publication “Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform” by researchers at University of Bern, this paper comments on the “dual-use” problem and regulation issue of synthetic biology from the perspective of responsible (research and) innovation, biosafety and biosecurity. Based on the ethical and legal framework, the authors suggest to conduct such research with high potential risks prudently and responsibly.

negative: Diseases of the Liver and Hepatobiliary System

negative: Estimate of the development of the epidemic reproduction number Rt from Coronavirus SARS-CoV-2 case data and implications for political measures based on prognostics The novel Coronavirus SARS-CoV-2 (CoV) has induced a world-wide pandemic and subsequent non-pharmaceutical interventions (NPI) in order to control the spreading of the virus. NPIs are considered to be critical in order to at least delay the peak number of infected individuals and to prevent the health care system becoming overwhelmed by the number of patients to treat in hospitals or in intensive care units (ICUs). However, there is also increasing concern that the NPIs in place would increase mortality because of other diseases, increase the frequency of suicide and increase the risk of an economic recession with unforeseeable implications. It is therefore instrumental to evaluate the necessity of NPIs and to monitor the progress of containment of the virus spreading. We used a data-driven estimation of the evolution of the reproduction number for viral spreading in Germany as well as in all its federal states. Based on an extended infection-epidemic model, parameterized with data from the Robert Koch-Institute and, alternatively, with parameters stemming from a fit to the initial phase of CoV spreading in different regions of Italy, we consistently found that the reproduction number was turned down to a range near 1 in all federal states. We used the latest reproduction number as a starting point for the simulation of epidemic progression and varied the reproduction number, mimicking either release or strengthening of NPIs. Germany is currently, April 3rd, 2020, at the border line of a reproduction number between the scenarios of major immunisation of the population or eradication of the virus. We strongly recommend to keep all NPIs in place and suggest to even strengthen the measures in order to accelerate reaching the state of full control, thus, also limiting collateral damage of the NPIs in time.

negative: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.

negative: Clinical considerations for patients with diabetes in times of COVID-19 epidemic

negative: Well-Being and the Good Death The philosophical literature on well-being and the good life contains very little explicit discussion of what makes for a better or worse death. The purpose of this essay is to highlight some commonly held views about the good death and investigate whether these views are recognized by the leading theories of well-being. While the most widely discussed theories do have implications about what constitutes a good death, they seem unable to fully accommodate these popular good death views. I offer two partial explanations for why these views have been neglected in discussions of well-being and make two corresponding recommendations for future work in the philosophy of well-being.

negative: PACT: Privacy Sensitive Protocols and Mechanisms for Mobile Contact Tracing The global health threat from COVID-19 has been controlled in a number of instances by large-scale testing and contact tracing efforts. We created this document to suggest three functionalities on how we might best harness computing technologies to supporting the goals of public health organizations in minimizing morbidity and mortality associated with the spread of COVID-19, while protecting the civil liberties of individuals. In particular, this work advocates for a third-party free approach to assisted mobile contact tracing, because such an approach mitigates the security and privacy risks of requiring a trusted third party. We also explicitly consider the inferential risks involved in any contract tracing system, where any alert to a user could itself give rise to de-anonymizing information. More generally, we hope to participate in bringing together colleagues in industry, academia, and civil society to discuss and converge on ideas around a critical issue rising with attempts to mitigate the COVID-19 pandemic.

negative: Responding to Covid-19 - A Once-in-a-Century Pandemic?

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: Three Emerging Coronaviruses in Two Decades: The Story of SARS, MERS, and Now COVID-19

negative: Pursuing a Good Death in the Time of COVID-19.

negative: Covid-19 predictions using a Gauss model, based on data from April 2 We propose a Gauss model (GM), a map from time to the bell-shaped Gauss function to model the casualties per day and country, as a quick and simple model to make predictions on the coronavirus epidemic. Justified by the sigmoidal nature of a pandemic, i.e. initial exponential spread to eventual saturation, we apply the GM to the first corona pandemic wave using data from 25 countries, for which a sufficient amount of not yet fully developed data exists, as of April 2, 2020, and study the model's predictions. We find that logarithmic daily fatalities caused by Covid-19 are well described by a quadratic function in time. By fitting the data to second order polynomials from a statistical chi2-fit with 95% confidence, we are able to obtain the characteristic parameters of the GM, i.e. a width, peak height and time of peak, for each country separately. We provide evidence that this supposedly oversimplifying model might still have predictive power and use it to forecast the further course of the fatalities caused by Covid-19 per country, including peak number of deaths per day, date of peak, and duration within most deaths occur. While our main goal is to present the general idea of the simple modeling process using GMs, we also describe possible estimates for the number of required respiratory machines and the duration left until the number of infected will be significantly reduced.

negative: The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?

negative: First COVID-19 suicide case in Bangladesh due to fear of COVID-19 and xenophobia: Possible suicide prevention strategies

negative: 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.

negative: Cancer and COVID-19; how do we manage cancer optimally through a public health crisis?

negative: The coronavirus disease 2019 (COVID-19) pandemic: A review and an update on cases in Africa The world has experienced several epidemics posing serious threat to global public health, including the 2002 severe acute respiratory syndrome (SARS) epidemic that caused 800 deaths out of about 8 000 cases, the 2009 H1N1 pandemic with 18 500 deaths, the 2012 Middle East respiratory syndrome (MERS) epidemic that caused 800 deaths out of 2 500 cases, the 2014 Ebola outbreak with 28 616 cases and 11 310 deaths, and the current coronavirus disease (COVID-19) pandemic with more than 35 000 deaths out of over 730 000 confirmed cases till now. Emerging infectious diseases continue to infect and reduce human populations. The COVID-19 pandemic has spread to more than 114 countries before it was officially declared as a pandemic by the WHO on the 11thMarch 2020. Here, the first set of index cases in Africa, and the differences between SARS-CoV-2 and other coronaviruses in addition to the preventive strategies on the emergence of COVID-19 were reviewed.

negative: Patterns of mortality during pandemic: An example of Spanish flu pandemic of 1918 Now the attention of the whole world is focused on the developing pandemic of the coronavirus infection COVID-19. This article discusses mortality patterns of the deadliest epidemic in the last 120 years – the Spanish flu pandemic of 1918. Statistical sources from Italy and the USA, published shortly after the pandemic, were analyzed. The analysis was carried out for mortality from all causes, since in this case inaccuracies associated with establishing the causes of death are minimized. Despite the fact that the first cases of the Spanish flu appeared in the United States as early as March 1918, this first wave of epidemic practically did not affect the total mortality rate. The main peak of mortality in 1918 occurred in October 1918 both in the USA and Italy, with a gradual decrease in mortality over several months. Analysis of age-specific mortality demonstrates a significant increase in mortality at middle ages (20–50 years) in 1918 compared with 1917. Analysis of mortality trends using the method of latent variables shows a significant increase in the background mortality factor in 1918, which turned out to be higher for Italy than the mortality losses during the Second World War. The Spanish flu pandemic differs from the current coronavirus pandemic, because of significant increase in mortality of middle-aged people, while the COVID-19 pandemic causes a more marked increase in mortality among the elderly. With this, the COVID-19 pandemic is more like the recent flu epidemics than the earlier Spanish flu pandemic.

negative: Replication of SARS-CoV-2 in human respiratory epithelium SARS-CoV-2 emerged by the end of 2019 to rapidly spread in 2020. At present, it is of utmost importance to understand the virus biology and to rapidly assess the potential of existing drugs and develop new active compounds. While some animal models for such studies are under development, most of the research is carried out in the Vero E6 cells. Here, we propose fully differentiated human airway epithelium cultures as a model for studies on the SARS-CoV-2. Further, we also provide basic characteristics of the system.

negative: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response Abstract Background and aim As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. Method We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. Results We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. Conclusion In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.

negative: Compassionate use of others’ immunity — understanding gut microbiome in Covid-19

negative: Viral Load Distribution in SARS Outbreak An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribution. Higher nasopharyngeal viral load was found in patients living in adjacent units of the same block inhabited by the index patient, while a lower but detectable nasopharyngeal viral load was found in patients living further away from the index patient. This pattern of nasopharyngeal viral load suggested that airborne transmission played an important part in this outbreak in Hong Kong. Contaminated fomites and rodent pests may have also played a role.

negative: El síndrome respiratorio agudo grave: primera pandemia del siglo XXI

negative: Uncharakteristisches Fieber (UF), afebrile Allgemeinreaktion (AFAR), Luftwegekatarrhe, Tonsillitis In diesem Kapitel werden jene Fälle behandelt, die diagnostisch und therapeutisch eng zusammengehören und die sich durch ihre überragende Häufigkeit auszeichnen.

negative: Coronavirus disease (COVID‐19) and neonate: What neonatologist need to know Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) cause china epidemics with high morbidity and mortality, the infection has been transmitted to other countries. About three neonates and more than 230 children cases are reported. The disease condition of the main children was mild. There is currently no evidence that SARS‐CoV‐2 can be transmitted transplacentally from mother to the newborn. The treatment strategy for children with Coronavirus disease (COVID‐19) is based on adult experience. Thus far, no deaths have been reported in the pediatric age group. This review describes the current understanding of COVID‐19 infection in newborns and children.

negative: Chinese Health Care Workers and COVID-19: For Whom the Bell Tolls

negative: Chapter 6 The immunosuppressed traveler: infection risks with autoimmunity and immunosuppression, vaccinations, and general travel advice Abstract The travel-related infection risks in the significantly immunocompromised traveler are complex and comprise vaccine preventable, vector-borne, and other nonvaccine preventable infections. A thorough risk assessment should be performed before travel and advice sought from relevant specialists. Immunosuppression used to treat autoimmune diseases and their mechanisms of action need particular consideration.This risk assessment needs to take the patient's beliefs and preferences into account. It is also important not to neglect noninfectious travel considerations.

negative: Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes. We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea. We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.

negative: Risikomanagement besonderer Infektionssituationen The WHO considers that there is considerable danger of an influenza pandemic. One result of globalisation is that other highly contagious infectious diseases, such as SARS or Ebola, which are potentially endemic, can also be brought into Germany. Bioterorrism must also be considered. As well as all other medical disciplines, hospital surgical departments must be armed against this now. National pandemic planning will be taken as an example to illustrate the planning needed in hospitals to prepare for emergencies arising from infections in such specific situations.

negative: Prediction of New Coronavirus Infection Based on a Modified SEIR Model BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation. METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases. RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1. CONCLUSIONS Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.

negative: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).

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: Modeling the transmission of new coronavirus in S\~ao Paulo State, Brazil -- Assessing epidemiological impacts of isolating young and elder persons We developed a mathematical model to describe the transmission of new coronavirus in the S\~ao Paulo State, Brazil. The model divided a community in subpopulations comprised by young and elder persons, in order to take into account higher risk of fatality among elder persons with severe CoViD-19. From data collected in the S\~ao Paulo State, we estimated the transmission and additional mortality rates, from which we calculated the basic reproduction number R0. From estimated parameters, estimation of the deaths due to CoViD-19 was three times lower than those found in literature. Considering isolation as a control mechanism, we varied isolation rates of young and elder persons in order to assess their epidemiological impacts. The epidemiological scenarios focused mainly on evaluating the number of severe CoViD-19 cases and deaths due to this disease when isolation is introduced in a population.

negative: Tail Risk of Contagious Diseases Applying a modification of Extreme value Theory (thanks to a dual distribution technique by the authors on data over the past 2,500 years, we show that pandemics are extremely fat-tailed in terms of fatalities, with a marked potentially existential risk for humanity. Such a macro property should invite the use of Extreme Value Theory (EVT) rather than naive interpolations and expected averages for risk management purposes. An implication is that potential tail risk overrides conclusions on decisions derived from compartmental epidemiological models and similar approaches.

negative: Development of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assays Targeting SARS-CoV-2 Epidemics of Coronavirus Disease 2019 (COVID-19) now have more than 100,000 confirmed cases worldwide. Diagnosis of COVID-19 is currently performed by RT-qPCR methods, but the capacity of RT-qPCR methods is limited by its requirement of high-level facilities and instruments. Here, we developed and evaluated RT-LAMP assays to detect genomic RNA of SARS-CoV-2, the causative virus of COVID-19. RT-LAMP assays in this study can detect as low as 100 copies of SARS-CoV-2 RNA. Cross-reactivity of RT-LAMP assays to other human Coronaviruses was not observed. We also adapted a colorimetric detection method for our RT-LAMP assay so that the tests potentially performed in higher throughput.

negative: Clinical research progresss of antiviral drugs for the novel coronavirus pneumonia/ 中华实验和临床病毒学杂志 The novel coronavirus (2019-nCoV or SARS-CoV-2) is a highly contagious and deadly virus that has infected more than 50 000 people and killed more than 1 000 people in 25 countries around the world. People who infected by the novel coronavirus may suffer from fever and cough, some may gradually appear breathing difficulties and other serious manifestations, some severe patients may have acute respiratory distress syndrome and septic shock leading to death. However, there are no definite and effective antiviral drugs for the novel coronavirus pneumonia all around the world. Therefore, this article aims to provide new idea for the effective treatment of the novel coronavirus pneumonia by summarizing the basic research and clinical progress of antiviral drugs at home and abroad.

negative: Large-scale evolutionary surveillance of the 2009 H1N1 influenza A virus using resequencing arrays In April 2009, a new influenza A (H1N1 2009) virus emerged that rapidly spread around the world. While current variants of this virus have caused widespread disease, particularly in vulnerable groups, there remains the possibility that future variants may cause increased virulence, drug resistance or vaccine escape. Early detection of these virus variants may offer the chance for increased containment and potentially prevention of the virus spread. We have developed and field-tested a resequencing kit that is capable of interrogating all eight segments of the 2009 influenza A(H1N1) virus genome and its variants, with added focus on critical regions such as drug-binding sites, structural components and mutation hotspots. The accompanying base-calling software (EvolSTAR) introduces novel methods that utilize neighbourhood hybridization intensity profiles and substitution bias of probes on the microarray for mutation confirmation and recovery of ambiguous base queries. Our results demonstrate that EvolSTAR is highly accurate and has a much improved call rate. The high throughput and short turn-around time from sample to sequence and analysis results (30 h for 24 samples) makes this kit an efficient large-scale evolutionary biosurveillance tool.

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: Maintenance Hemodialysis and Coronavirus Disease 2019 (COVID-19): Saving Lives With Caution, Care, and Courage

negative: Does the Bacillus Calmette–Guérin vaccine provide protection from COVID-19? OBJECTIVE: The novel coronavirus pandemic is ravaging throughout the world. It has infected more than 1.2 million people and killed more than 64,000. Frantic research is underway to find prevention and cure. Of late, Bacillus Calmette–Guérin (BCG) has been speculated as a possible protection from COVID-19. We sought to investigate the evidence behind the claim. MATERIAL AND METHODS: Data were collected regarding the total number of COVID-19 cases per million and total number of COVID-19 deaths per million in various countries. The BCG vaccination policies of these countries were also obtained. RESULTS: It was seen that the countries with no universal BCG policy had a mean 1272.9 (median 795) cases per million and 80.7 deaths (median 18) per million population. On the contrary, the countries with a universal BCG vaccination policy had a mean 131.2 (median 40) cases per million and 4 deaths (median 1) per population. The difference is highly significant (P < 0.001). CONCLUSION: The data strongly support the hypothesis that BCG may offer protection from COVID-19. Heterologous protection offered by BCG through production of trained immunity, epigenetic reprogramming of monocytes, non-specific activation of NK cells, and increase of pro-inflammatory cytokines (particularly, tumor necrosis factor [TNF]-alpha and interleukin 1 beta) production may be the mechanism behind its cross- protection against the novel coronavirus.

negative: Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements Abstract The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.

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: The within-host viral kinetics of SARS-CoV-2 In this work, we use a within-host viral dynamic model to describe the SARS-CoV-2 kinetics in host. Chest radiograph score data are used to estimate the parameters of that model. Our result shows that the basic reproductive number of SARS-CoV-2 in host growth is around 3.79. Using the same method we also estimate the basic reproductive number of MERS virus is 8.16 which is higher than SARS-CoV-2. The PRCC method is used to analyze the sensitivities of model parameters and the drug effects on virus growth are also implemented to analyze the model.

negative: What we know about 2019-nCoV in Iran in the early stage? On 10 January 2020, a new coronavirus causing a pneumonia outbreak spread rapidly in all of the World. On 19 February 2020, the first official announcement of death from 2019-Nov was made in Iran. As of 7 March 2020, there were 101,927 confirmed cases of Covid-19 infection, including 3486 deaths, reported in the World. In the eastern and Mediterranean region Iran with 4747 confirmed cases of Covid-19 infection and 124 deaths, is in the critical stage. Therefore, there is a matter of urgency combating this new virus and stopping the epidemic. Here, we focus on symptoms and the development of fast diagnosis methods, as well as potential management to prevent or treat the Covid-19 infection.

negative: Comparison Between Balloon-Assisted and Stent-Assisted Technique for Treatment of Unruptured Internal Carotid Artery Aneurysms. PURPOSE To compare clinical and angiographic outcomes between balloon-assisted (BAC) and stent-assisted coiling for internal carotid artery unruptured aneurysms (ICA-UA). MATERIALS AND METHODS A total of 227 ICA-UA in 190 patients were treated with BAC (120 patients, 141 ICA-UA) or SAC (70 patients, 86 ICA-UA. We compared characteristics of patients and ICA-UA, and clinical and angiographic outcomes between groups. RESULTS Aneurysm size and neck diameter were greater for SAC than in BAC, but aneurysm volume and coil packing density were not different between groups. Immediate angiographic occlusion grade was better for BAC than for SAC. Periprocedural thromboembolic events were more frequent during SAC (11.6%) than BAC (2.4%) per aneurysm, but hemorrhagic events were the opposite (2.4% for BAC and none for SAC per aneurysm) (p < 0.05). At discharge, treatment-related morbi-mortality rates were 1.6% for BAC and 1.4% per patient for SAC. At clinical follow-up (BAC, 118 patients [98.3%] for a mean of 48.4 months; SAC, 69 patients [98.6%], for a mean of 37.4 months), 1 additional treatment-related infarction occurred during SAC, resulting in a modified Rankin scale score of 4. Thus, overall treatment-related morbi-mortality rates were 1.7% in BAC and 2.9% in SAC. At imaging follow-up (BAC, 135 aneurysms [95.7%] for 28.3 months; SAC, 81 aneurysms [94.1%] for 23.9 months), BAC and SAC showed stable or improved occlusion in 94.1% and 95.0%, minor recurrence in 4.4% and 2.5%, and major recurrence in 1.5% and 2.5%, respectively. CONCLUSION Both BAC and SAC were safe and effective techniques for ICA-UA. There were no differences in morbi-mortality and recurrence rates between groups.

negative: Impact of community respiratory viral infections in urban children with asthma Abstract Background Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. Objective We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. Methods We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. Results Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. Conclusion Urban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.

negative: The proportion of deaths cases in confirmed patients of COVID-19 is still increasing for cumulative cases reported up to 25 April 2020 In this work I analyse how proportions of fatal cases after COVID-19 infection change since outbreak of the disease. Using publicity available data I model the change in deaths probability from day 30 of outbreak until 25 April 2020. The global trend is that the proportion of fatal cases is still increasing and that many countries have not yet reached the maximum deaths proportion. However, there are visual differences between countries and in some countries the proportions are clearly below or above the global trend. A positive correlation between deaths cases and recorded infections indicates that a higher infection number results in increased mortality numbers.

negative: Host deadenylation-dependent mRNA decapping factors are required for a key step in brome mosaic virus RNA replication. The genomes of positive-strand RNA [+RNA] viruses perform two mutually exclusive functions: they act as mRNAs for the translation of viral proteins and as templates for viral replication. A universal key step in the replication of +RNA viruses is the coordinated transition of the RNA genome from the cellular translation machinery to the viral replication complex. While host factors are involved in this step, their nature is largely unknown. By using the ability of the higher eukaryotic +RNA virus brome mosaic virus (BMV) to replicate in yeast, we previously showed that the host Lsm1p protein is required for efficient recruitment of BMV RNA from translation to replication. Here we show that in addition to Lsm1p, all tested components of the Lsm1p-7p/Pat1p/Dhh1p decapping activator complex, which functions in deadenylation-dependent decapping of cellular mRNAs, are required for BMV RNA recruitment for RNA replication. In contrast, other proteins of the decapping machinery, such as Edc1p and Edc2p from the deadenylation-dependent decapping pathway and Upf1p, Upf2p, and Upf3p from the deadenylation-independent decapping pathway, had no significant effects. The dependence of BMV RNA recruitment on the Lsm1p-7p/Pat1p/Dhh1p complex was linked exclusively to the 3' noncoding region of the BMV RNA. Collectively, our results suggest that the Lsm1p-7p/Pat1p/Dhh1p complex that transfers cellular mRNAs from translation to degradation might act as a key regulator in the switch from BMV RNA translation to replication.

negative: I Just Can’t Get Enough (of Experts): The Numbers of COVID-19 and the Need for a European Approach to Testing This article offers a reflection on the testing strategies deployed in the generation of epidemiological data in the European Union (EU). I will argue that, while in the early days of the pandemic, Member States proceeded to testing in a rather scattered way, the shortage of resources seems to have acted as a driver of coordination, which is now increasingly being discussed at EU level. I will examine the legal and institutional framework supporting such embryonic coordination efforts and offer a preliminary assessment of their implications for a European approach to epidemiological knowledge-making.

negative: Can judgments according to case fatality rate be correct all the time during epidemics? Estimated cases based on CFR in different scenarios and some lessons from early case fatality rate of coronavirus disease 2019 in Iran Background: The new Coronavirus disease (COVID-19) was first identified in China in 2019. Case fatality rate (CFR) indicator of the disease is one of the most important indices noticed by experts, policymakers, and managers, based on which daily evaluations and many judgments are made. CFR can change during epidemics. This study aimed to estimate the actual number of COVID-19 cases in Iran and to calculate the early CFR for the disease based on official statistics. Methods: This was a descriptive study whose data were obtained from the website of the Ministry of Health and Medical Education of Iran from February 20, 2020 until March 26, 2020. CFR has been obtained by dividing the total number of deaths by the total number of confirmed cases at one point in time. In this study, the actual number of COVID-19 cases in Iran was estimated based on the mortality model in 4 scenarios. Excel 2013 software was used to analyze the data. Results: According to the findings of this study, In Iran, until March 26, 2020, a total of 27 017 people have been infected by COVID-19 and 2077 died of it. However, CFR indicator had a descending trend in Iran: 100%, 18.6%, 8.8%, 3.3%, 6.9%, and 7.7% on days 1, 5, 10, 20, 30, and 35, respectively. The actual number of COVID-19 cases in Iran was estimated to be 4 789 454, 2 873 673, 1 436 836, and 718418 as of March 26, 2020 according to the 4 scenarios, respectively. Conclusion: In emerging epidemics, CFR indicator must not be used as a basis to judge the performance of a health system unless that epidemic condition has been clarified. Moreover, it is suggested that in the outbreak of an epidemic, specifically emerging diseases, CFR must not be the base of judgment. Making judgments, specifically in the outbreak of emerging epidemics, based on fatality rate can lead to information bias. It is also possible to estimate the total number of patients based on the CFR in circumstances where little information is available on the disease.

negative: Have deaths from COVID-19 in Europe plateaued due to herd immunity?

negative: Psychological responses, behavioral changes and public perceptions during the early phase of the COVID-19 outbreak in China: a population based cross-sectional survey Objective: To investigate psychological and behavioral responses to the threat of SARS-CoV-2 infections and their associations with public perceptions in China Design: Cross sectional population-based telephone survey via random digital dialing between 1 and 10 February, 2020 Setting: Wuhan (the epicentre and quarantined city), and Shanghai (a typical major city with close transportation link with Wuhan) Participants: Random sample of 510 residents in Wuhan and 501 residents in Shanghai aged above 18 Main outcome measures: Anxiety (measured by the 7-item generalized anxiety disorder [GAD-7] scale), recommended and avoidance behaviors (engaged in all six behaviors such as increasing surface cleaning and reducing going out). Results: The prevalence rates of moderate or severe anxiety (score ≥10 on GAD-7) were 32.7% (n=167) among Wuhan participants and 20.4% (n=102) among Shanghai participants. 78.6% (n=401) of Wuhan participants and 63.9% (n=320) of Shanghai participants had carried out all six precautionary behaviors. For both measures, Wuhan participants were more responsive to the outbreak (p<0.001). Controlling for personal characteristics, logistic regression results suggested that risks of moderate or severe anxiety were positively associated with perceived susceptibility (odds ratio 1.6, 95% confidence interval 1.3-1.8) and severity of the disease (1.6, 1.4-1.9) and confusion about information reliability (1.6, 1.5-1.9). Having confidence in taking measures to protect oneself against the disease was associated with a lower risk (0.6, 0.5-0.7). The strongest predictor of behavioral change was perceived severity (1.2, 1.1-1.4), followed by confusion about information reliability (1.1, 1.0-1.3). Conclusions: Psychological and behavioral responses to COVID-19 have been dramatic during the rising phase of the outbreak. Our results support efforts for timely dissemination of accurate and reliable information to address the high anxiety level.

negative: Dying in the face of the COVID-19 pandemic: Contextual considerations and clinical recommendations. Dying is a natural part of life; however, death is often a fearful, frightening event. Dying in the midst of the COVID-19 pandemic presents challenges that magnify normative fears and may interfere with a healthy grieving process. To maintain a resilient spirit among those who are at risk of losing a loved one or who have lost a family member to COVID-19, it is important that they be provided with the necessary contextually and culturally appropriate skills and resources to facilitate healing in the face of hardship and uncertainty. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: Nursing homes or besieged castles: COVID-19 in northern Italy

negative: Corona-Krise: (Wirtschafts-)politische Perspektiven: Die Reflexe aus der Finanzkrise sind nicht genug! The explosion of Covid-19 cases is looming in Germany. The German Society for Epidemiology has warned that the number of cases could soon overshoot the capacity of the healthcare system. This may be true even if Germany follows the ‘flatten-the-curve’- approach to reduce infection rates. A suppression of the virus remains the best solution for the crisis. Supply will suffer as long the virus persists. Until then, demand side measures will not cure the epidemic. Coordinated measures for business that ensure compliance and European debt instruments may be part of a strategy to solve the crisis.

negative: Worldwide and Regional Forecasting of Coronavirus (Covid-19) Spread using a Deep Learning Model In December 2019, Covid-19 epidemic was identified in Wuhan, China. Covid-19 may cause fatality especially among elderly, and people with chronic health problems. After human to human transmissions of the disease, it has rapidly spread throughout China, and then the outbreak has reached to neighboring countries in Asia. Now, the spread of the virus is accelerating in the world, and increasing number of new cases has been reported daily in Europe, Middle East, Africa and America regions. Recently, World Health Organization (WHO) also announced Covid-19 as a Pandemic. As of 3 April, worldwide around more than 1 million cases and around 60,000 fatalities are reported. Thus, forecasting regional and worldwide outbreak size of Covid-19 is important in order to take necessary actions regarding to preparedness plans and mitigation interventions. In this work, we design a deep learning model, which is an effective artificial intelligence method, to provide regional and worldwide forecasts. Particularly for worldwide, our approach predicts the cumulative number of cases, cumulative number of deaths and daily new cases. For Europe and Middle East regions, we predict the cumulative number of cases, and for Mainland China we predict daily new cases and the cumulative number of deaths. We predict the next 10 days based on the previously reported actual time series data of Covid-19. For worldwide forecasts, we use the data provided by Worldometers. For Europe and Middle East forecasts, we use the data provided by World Health Organization, and for China Mainland forecasts, the data is obtained from Chinese Centre for Disease Control and Prevention. This is the first time that a deep learning model has been employed for Covid-19 spread prediction, solely based on the known reported cases of Covid-19. The proposed deep learning architecture consists of Long Short Term Memory (LSTM) layer, dropout layer, and fully connected layers to predict regional and worldwide forecasts. We evaluate our approach with Root Mean Square Error (RMSE) metric. For forecasting, we use the network models that give the minimum RMSE on the last 3 days of actual data. Networks, which achieves the minimum RMSE on the last 3 days, are used to predict the next 10 days. Every day, the spread and situations are changing. Our approach can take into account these real-time changes; the deep learning model can be re-trained with new daily data and perform real-time forecasting. Results show that the proposed deep learning model is promising, it can predict possible scenarios regionally and globally for the spread of Covid-19.

negative: Why does the coronavirus spread so easily between people?

negative: Self-harm and COVID-19 Pandemic: An emerging concern – A report of 2 cases from India

negative: Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19 Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4-14) days for the HCQ and NHCQ groups, respectively (P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL-1 at the beginning of the treatment to 5.2 (3.0-23.4) pg mL-1 (P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives. hydroxychloroquine, IL-6, mortalities, COVID-19.

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: Differential susceptibility of cultured neural cells to the human coronavirus OC43. By using cell-type-specific markers and neural cultures derived from various areas of the nervous system, it has been possible to identify various interactions between OC43 virus and mouse oligodendrocytes, neurons, astrocytes, and fibroblasts. Neurons derived from dorsal root ganglia produced viral antigen and infectious virus. Astrocytes and fibroblasts both produced viral antigen but not infectious virus. Oligodendrocytes produced neither infectious virus nor viral antigen. Human embryo brain cells, including astrocytes, were susceptible to OC43 infection but did not produce infectious virus.

negative: Criterios de ingreso hospitalario de los pacientes con una enfermedad pulmonar obstructiva crónica

negative: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales. The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially 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 difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess 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: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC(50)) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC(50) concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC(50)s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.

negative: Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world’s health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter’s search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms (“corona,” “2019-nCov,” and “COVID-19”), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news.

negative: Coronavirus Perceptions And Economic Anxiety We provide one of the first systematic assessments of the development and determinants of economic anxiety at the onset of the coronavirus pandemic. Using a global dataset on internet searches and two representative surveys from the US, we document a substantial increase in economic anxiety during and after the arrival of the coronavirus. We also document a large dispersion in beliefs about the pandemic risk factors of the coronavirus, and demonstrate that these beliefs causally affect individuals' economic anxieties. Finally, we show that individuals' mental models of infectious disease spread understate non-linear growth and shape the extent of economic anxiety.

negative: What led to the UK's COVID-19 death toll? - An insight into the mistakes made and the current situation

negative: 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.)

negative: Recent advances of therapeutic targets and potential drugs of COVID-19 Since December 2019, numerous cases of coronavirus disease 2019 (COVID-19) caused by the infection of the novel coronavirus (2019-nCoV) have been confirmed in Wuhan, China. The outbreak of 2019-nCoV in China embodied a significant and urgent threat to global health. 2019-nCoV was a new, highly contagious coronavirus discovered following the outbreak of SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV). The novel coronavirus can cause severe respiratory disease and even death. However, no specific therapeutic drugs have been developed clinically thus far. This article examines the potential of therapeutic drugs by assessing the structure of 2019-nCoV, its mechanism in invading host cells, and the anti-viral mechanism of the human autoimmune system. We also review the latest research regarding the progress of potential therapeutic drugs and provide references for new drug developments of COVID-19.

negative: Proximal femur fractures in COVID-19 emergency: the experience of two Orthopedics and Traumatology Departments in the first eight weeks of the Italian epidemic INTRODUCTION: CoVID-19 (Coronavirus disease) is a worldwide infection which is causing millions of deaths. A significant number of elderly patients require hospitalization and develop serious and sometimes life-threatening complications. The aim of this study is to evaluate the preliminary impact (8 weeks) of CoVID-19, focusing on proximal femur fractures, analyzing data and results compared to the same period of 2019. MATERIALS AND METHODS: From February 22nd to April 18th, 2020 we surgically treated 121 proximal femur fractures (61 in Piacenza; 60 in Parma, 16 male, 44 female, mean age 81.1). In the same period of 2019, we treated 169 proximal femur fractures (90 in Piacenza, 33 male, 57 female, mean age 81.9; 79 in Parma, 29 males, 50 female, mean age 80.2). We had 21/61 (34.4%) patients resulted positive for COVID-19 and 11/61 in Parma (18.3%), based on nasal-pharyngeal swab, chest CT scan and/or lung US findings. RESULTS: The incidence of proximal femur fractures had a significant reduction during CoVID-19 spread in Piacenza and Parma. Authors have noticed an elevated number of deaths within 21 days after surgery. Piacenza: 4 cases in 2019 (4.4%) and 11 in 2020 (18.0%), of which 9 cases CoVID positive. In Parma in 2019 two deaths were encountered; in 2020 6 patients died and 5 cases were CoVID positive. CONCLUSION: In the first two months of the Italian epidemic, in the cities of Piacenza and Parma over 80% of deaths have occurred in patients over 70 years old. Even if preliminary, our study shows a significant increase in death in elderly patients surgically treated for proximal femur fractures, particularly in the Piacenza Hospital.

negative: Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5' mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR- and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.

negative: The Globalization of Healthcare: Implications of Medical Tourism for the Infectious Disease Clinician Travel abroad for healthcare has increased rapidly; interventions include organ transplant; cardiac surgery; reproductive care; and joint, cosmetic, and dental procedures. Individuals who receive medical care abroad are a vulnerable, sentinel population, who sample the local environment and can carry home unusual and resistant infections, documented in many reports. Medical tourists are at risk for hospital-associated and procedure-related infections as well as for locally endemic infections. Patients may not volunteer details about care abroad, so clinicians must inquire about medical procedures abroad as well as recent travel. Special infection control measures may be warranted. Healthcare abroad is associated with diverse financial, legal, ethical, and health-related issues. We focus on problems the infectious disease clinician may encounter and provide a framework for evaluating returned medical tourists with suspected infections. A better system is needed to ensure broad access to high-quality health services, continuity of care, and surveillance for complications.

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: Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China. Methods We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between-country connectivity. Results We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country. Conclusions As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.

negative: Up to 2.2 million people experiencing disability suffer collateral damage each day of Covid-19 lockdown in Europe BACKGROUND: The Covid-19 pandemic is having a great impact on health services. Patients not receiving care due to closure of outpatient services suffer a collateral damage. Our aim was to provide first data on impact of Covid-19 on people experiencing disability in Europe. METHODS: We developed an estimation from a survey and publicly available data. Thirty-eight countries have been inquired through the European Bodies of Physical and Rehabilitation Medicine - the rehabilitation medical specialty. The 9-questions focused on March 31st, 2020. We used the following indicators: for inpatients, acute and rehabilitative hospital beds; for outpatients, missing uniform European data, we used information from Italy, Belgium and UK, and estimated for Europe basing on population, number of rehabilitation physicians, physiotherapists, and people with self-reported limitations. FINDINGS: Thirty-five countries (92%) including 99% of the population (809.9 million) answered. Stop of admissions to rehabilitation, early discharge and reduction of activities involved 194,800 inpatients in 10 countries. Outpatient activities stopped for 87%, involving 318,000 patients per day in Italy, Belgium and UK, leading to an estimate range of 1,3-2,2 million in Europe. Seven countries reported experiences on rehabilitation for acute Covid-19 patients. INTERPRETATION: Covid-19 emergency is having a huge impact on rehabilitation of people experiencing disability. This may lead to future cumulative effects due to reduced functional outcome and consequent increased burden of care. When the emergency will fade, rehabilitation demand will probably grow due to an expected return wave of these not well treated patients, but probably also of post-Covid-19 patients' needs.

negative: The first three months of the COVID-19 epidemic: Epidemiological evidence for two separate strains of SARS-CoV-2 viruses spreading and implications for prevention strategies About one month after the COVID-19 epidemic peaked in Mainland China and SARS-CoV-2 migrated from China westward to Europe and then the U.S., the epidemiological data begin to provide important insights into the risks associated with the disease and the effectiveness of intervention strategies. Like other respiratory diseases, including the 2003 SARS epidemic, the virus remains only about two months in any given population, yet the peak incidence and the lethality can vary. The data suggest that at least two strains of the 2020 SARS-CoV-2 virus have evolved during its migration from Mainland China to Europe. South Korea, Iran, and Italy were hit by the more dangerous "SKII" variant. While the epidemic in China is about to end, and in Europe about to level off, the course of the epidemic in the younger US population is still increasing and the peak level will likely depend on which of the strains has entered the US first. The same models that help us to understand the epidemic also help us to choose prevention strategies. While containment merely prolongs the time the disease circulates until the proportion of immune people is high enough for "herd immunity", reducing disease severity, either by vaccination or by early treatment of complications, is the best strategy against a respiratory virus disease.

negative: Extracting COVID-19 Events from Twitter We present a corpus of 7,500 tweets annotated with COVID-19 events, including positive test results, denied access to testing, and more. We show that our corpus enables automatic identification of COVID-19 events mentioned in Twitter with text spans that fill a set of pre-defined slots for each event. We also present analyses on the self-reporting cases and user's demographic information. We will make our annotated corpus and extraction tools available for the research community to use upon publication at https://github.com/viczong/extract_COVID19_events_from_Twitter

negative: Emerging Animal Coronaviruses: First SARS and Now MERS The first major pandemic of the new millennium that arose from southern China in 2002 was of zoonotic origin from wild game animals, called severe acute respiratory syndrome [SARS]. The culprit was determined to be a coronavirus of animal origin [SARS-CoV]. The discovery of the SARS-CoV, which caused an outbreak of >8000 people in >30 countries with fatality of about 10%, resulted in intense search for novel coronaviruses with potentially high pathogenicity. Ten years later after the SARS pandemic, another novel coronavirus crossed the species barrier from bats to humans through an intermediate camel host, to produce a severe lower respiratory infection labeled the Middle East respiratory syndrome [MERS]. A novel coronavirus [MERS-CoV] was first identified in September 2012, from patients who resided or traveled to Saudi Arabia. The MERS-CoV spread through contacts with camel and subsequently from human to human via droplet transmission. MERS cases occurred in several other countries including in Europe and the United States, mainly from residence or travel to the Arabian Peninsula, but was not of pandemic potential. However, in the spring of 2015, a MERS outbreak started in South Korea which was initiated by a returning traveler from Saudi Arabia, and subsequently secondary infection of over 186 local residents occurred. Recent estimate in May 2015 indicates that the MERS-CoV have afflicted 1167 patients with MERS worldwide with 479 deaths [41% fatality]. Thus MERS is more deadly than SARS but appears to be less contagious. However, unlike SARS which has not reappeared since 2002–2003, MERS-CoV have the potential to cause sporadic or local outbreaks for many years as the virus may now be entrenched endemically in dromedary camels of the Middle East.

negative: Passengers' destinations from China: low risk of Novel Coronavirus (2019-nCoV) transmission into Africa and South America Novel Coronavirus (2019-nCoV [SARS-COV-2]) was detected in humans during the last week of December 2019 at Wuhan city in China, and caused 24 554 cases in 27 countries and territories as of 5 February 2020. The objective of this study was to estimate the risk of transmission of 2019-nCoV through human passenger air flight from four major cities of China (Wuhan, Beijing, Shanghai and Guangzhou) to the passengers' destination countries. We extracted the weekly simulated passengers' end destination data for the period of 1–31 January 2020 from FLIRT, an online air travel dataset that uses information from 800 airlines to show the direct flight and passengers' end destination. We estimated a risk index of 2019-nCoV transmission based on the number of travellers to destination countries, weighted by the number of confirmed cases of the departed city reported by the World Health Organization (WHO). We ranked each country based on the risk index in four quantiles (4(th) quantile being the highest risk and 1(st) quantile being the lowest risk). During the period, 388 287 passengers were destined for 1297 airports in 168 countries or territories across the world. The risk index of 2019-nCoV among the countries had a very high correlation with the WHO-reported confirmed cases (0.97). According to our risk score classification, of the countries that reported at least one Coronavirus-infected pneumonia (COVID-19) case as of 5 February 2020, 24 countries were in the 4(th) quantile of the risk index, two in the 3(rd) quantile, one in the 2(nd) quantile and none in the 1(st) quantile. Outside China, countries with a higher risk of 2019-nCoV transmission are Thailand, Cambodia, Malaysia, Canada and the USA, all of which reported at least one case. In pan-Europe, UK, France, Russia, Germany and Italy; in North America, USA and Canada; in Oceania, Australia had high risk, all of them reported at least one case. In Africa and South America, the risk of transmission is very low with Ethiopia, South Africa, Egypt, Mauritius and Brazil showing a similar risk of transmission compared to the risk of any of the countries where at least one case is detected. The risk of transmission on 31 January 2020 was very high in neighbouring Asian countries, followed by Europe (UK, France, Russia and Germany), Oceania (Australia) and North America (USA and Canada). Increased public health response including early case recognition, isolation of identified case, contract tracing and targeted airport screening, public awareness and vigilance of health workers will help mitigate the force of further spread to naïve countries.

negative: Mapping inhibitor binding modes on an active cysteine protease via nuclear magnetic resonance spectroscopy. Cruzain is a member of the papain/cathepsin L family of cysteine proteases, and the major cysteine protease of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We report an autoinduction methodology that provides soluble cruzain in high yields (>30 mg/L in minimal medium). These increased yields provide sufficient quantities of active enzyme for use in nuclear magnetic resonance (NMR)-based ligand mapping. Using circular dichroism and NMR spectroscopy, we also examined the solution-state structural dynamics of the enzyme in complex with a covalently bound vinyl sulfone inhibitor (K777). We report the backbone amide and side chain carbon chemical shift assignments of cruzain in complex with K777. These resonance assignments were used to identify and map residues located in the substrate binding pocket, including the catalytic Cys25 and His162. Selective [(15)N]Cys, [(15)N]His, and [(13)C]Met labeling was performed to quickly assess cruzain-ligand interactions for a set of eight low-molecular weight compounds exhibiting micromolar binding or inhibition. Chemical shift perturbation mapping verified that six of the eight compounds bind to cruzain at the active site. Three different binding modes were delineated for the compounds, namely, covalent, noncovalent, and noninteracting. These results provide examples of how NMR spectroscopy can be used to screen compounds for fast evaluation of enzyme-inhibitor interactions to facilitate lead compound identification and subsequent structural studies.

negative: Mitigating the air pollution effect? The remarkable decline in the pollution-mortality relationship in Hong Kong Abstract Using transboundary pollution from mainland China as an instrument, we show that air pollution leads to higher cardio-respiratory mortality in Hong Kong. However, the air pollution effect has dramatically decreased over the past two decades: before 2003, a 10-unit increase in the Air Pollution Index could lead to a 3.1% increase in monthly cardio-respiratory mortality, but this effect has declined to 0.5% using recent data and is no longer statistically significant. Exploratory analyses suggest that a well-functioning medical system and immediate access to emergency services can help mitigate the contemporaneous effects of pollution on mortality.

negative: Differential Diagnosis of Common Acute Toxicologic Versus Nontoxicologic Illness This table outlines common toxicologic versus nontoxicologic rule outs based on clinical abnormalities seen in an acutely ill animal. The purpose is to provide an initial guideline for considering toxicologic versus nontoxicologic rule outs when a patient is presented to a practicing veterinarian. Major clinical abnormalities followed by common toxicologic rule outs and non-toxicologic rule outs have been listed so that practicing veterinarians can narrow down an etiology quickly. Based on history, physical examination findings, and blood work changes, once a reasonable etiology has been narrowed down or established, the reader is encouraged to review a more detailed discussion on management of the particular poisoning or disease listed in this or other references.

negative: Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies The main objective of the present paper is twofold: first, to model the fatality curves of the COVID-19 disease, as represented by the cumulative number of deaths as a function of time; and second, to use the corresponding mathematical model to study the effectiveness of possible intervention strategies. We applied the Richards growth model (RGM) to the COVID-19 fatality curves from several countries, where we used the data from the Johns Hopkins University database up to April 1, 2020. Countries selected for analysis were China, Italy, Spain, Iran, and Brazil. The RGM was shown to describe very well the fatality curves of China, which is in a late stage of the COVID-19 outbreak, as well as of Italy, Spain, and Iran, which supposedly are in the middle of the outbreak at the time of this writing. As for Brazil, which is still in the so-called exponential growth regime, we used the generalized growth model which is more appropriate for such cases. An analytic formula for the efficiency of intervention strategies within the context of the RGM is derived. Our findings show that there is only a narrow window of opportunity, after the onset of the epidemic, during which effective countermeasures can be taken. We applied our intervention model to the COVID-19 fatality curve of Italy to illustrate the effect of several possible interventions.

negative: Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID-19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.

negative: SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China Summary Background Whether the patients with COVID-19 infected by SARS-CoV-2 would commonly develop acute renal function damage is a problem worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. Methods 116 hospitalized COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography (CT) scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was examined by real-time RT-PCR. Findings 12 (10.8%) and 8 (7.2%) patients showed mild elevation of blood urea nitrogen or creatinine, and trace or 1+ albuminuria respectively in 111 COVID-19-confirmed patients without basic kidney disease. In addition, 5 patients with chronic renal failure (CRF) were undergone regular continuous renal replacement therapy (CRRT) were confirmed infection of SARS-CoV-2, and diagnosed as COVID-19. Beside the treatment of COVID-19, CRRT was also applied three times weekly. The course of treatment, the renal function indicators showed stable, without exacerbation of CRF, and pulmonary inflammation was gradually absorbed. All 5 patients with CRF were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without renal illness before, and one patient had a positive for SARS-CoV-2 ORF 1ab from 5 cases with CRF. Interpretation Acute renal impairment was uncommon in COVID-19. SARS-CoV-2 infection does not significantly cause obvious acute renal injury, or aggravate CRF in the COVID-19 patients.

negative: Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1) On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.

negative: First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model BACKGROUND: Similar to outbreaks of many other infectious diseases, success in controlling the novel 2019 coronavirus infection requires a timely and accurate monitoring of the epidemic, particularly during its early period with rather limited data while the need for information increases explosively. METHODS: In this study, we used a second derivative model to characterize the coronavirus epidemic in China with cumulatively diagnosed cases during the first 2 months. The analysis was further enhanced by an exponential model with a close-population assumption. This model was built with the data and used to assess the detection rate during the study period, considering the differences between the true infections, detectable and detected cases. RESULTS: Results from the second derivative modeling suggest the coronavirus epidemic as nonlinear and chaotic in nature. Although it emerged gradually, the epidemic was highly responsive to massive interventions initiated on January 21, 2020, as indicated by results from both second derivative and exponential modeling analyses. The epidemic started to decelerate immediately after the massive actions. The results derived from our analysis signaled the decline of the epidemic 14 days before it eventually occurred on February 4, 2020. Study findings further signaled an accelerated decline in the epidemic starting in 14 days on February 18, 2020. CONCLUSIONS: The coronavirus epidemic appeared to be nonlinear and chaotic, and was responsive to effective interventions. The methods used in this study can be applied in surveillance to inform and encourage the general public, public health professionals, clinicians and decision-makers to take coordinative and collaborative efforts to control the epidemic.

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: Prediction of Peak and Termination of Novel Coronavirus Covid-19 Epidemic in Iran The growth and development of Covid-19 transmission have significantly cut the attention of many societies, particularly Iran that has been struggling with this contagious, infectious disease since late February 2020. In the present study, the known SIR model was used for the dynamics of an epidemic to provide a suitable assessment of the COVID-19 virus epidemic in Iran. The epidemic curve and SIR model parameters were obtained with the use of Iran statistical data. The recovered people were considered alongside the official number of confirmed victims as the reliable long-time statistical data of Iran. The results offered many important predictions of the COVID-19 virus epidemic such as realistic number of victims, infection rate, peak time, and other characteristics.

negative: Why do People Share Misinformation during the COVID-19 Pandemic? The World Health Organization have emphasised that misinformation - spreading rapidly through social media - poses a serious threat to the COVID-19 response. Drawing from theories of health perception and cognitive load, we develop and test a research model hypothesizing why people share unverified COVID-19 information through social media. Our findings suggest a person's trust in online information and perceived information overload are strong predictors of unverified information sharing. Furthermore, these factors, along with a person's perceived COVID-19 severity and vulnerability influence cyberchondria. Females were significantly more likely to suffer from cyberchondria, however, males were more likely to share news without fact checking their source. Our findings suggest that to mitigate the spread of COVID-19 misinformation and cyberchondria, measures should be taken to enhance a healthy skepticism of health news while simultaneously guarding against information overload.

negative: Effective Use of Angiotensin II in Coronavirus Disease 19–Associated Mixed Shock State: A Case Report The rapid spread of Coronavirus Disease 2019 (COVID-19) has sparked a search for effective therapies. The discovery that the virus binds the angiotensin-converting enzyme 2 (ACE2) receptor has led to investigation of the renin–angiotensin system for possible therapeutic targets. We present a case of an elderly woman with multiple comorbidities who developed severe acute respiratory distress syndrome (ARDS), a cardiomyopathy, and vasodilatory shock secondary to COVID-19 and was treated with exogenous angiotensin II. She rapidly demonstrated significant hemodynamic improvement without noted adverse effects. Thus, we propose further investigation into possible benefits of angiotensin II in shock secondary to COVID-19.

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: Considerations for Statin Therapy in Patients with COVID‐19 Current coronavirus pandemic named coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is the third coronavirus outbreak during the current century after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses.1 Acute respiratory distress syndrome (ARDS) is an immunopathologic event and main cause of death following COVID-19. The main mechanism of ARDS is uncontrolled systemic inflammatory response and cytokine storm following release of proinflammatory cytokines (such as interferons (IFN), interleukines (IL), tumor necrosis factor (TNF)-α) and chemokines.2-3 So, some Chinese researchers proposed or used anti-inflammatory agents in the treatment regimen of patients with COVID-19.3-4.

negative: Ecological Traits Driving the Outbreaks and Emergence of Zoonotic Pathogens Infectious diseases that are transmitted from wildlife hosts to humans, such as the Ebola virus and MERS virus, can be difficult to understand because the pathogens emerge from complex multifaceted ecological interactions. We use a wildlife–pathogen system—prairie dogs (Cynomys ludovicianus) and the plague bacterium (Yersinia pestis)—to describe aspects of disease ecology that apply to many cases of emerging infectious disease. We show that the monitoring and surveillance of hosts and vectors during the buildup to disease outbreaks are crucial for understanding pathogen-transmission dynamics and that a community-ecology framework is important to identify reservoir hosts. Incorporating multidisciplinary approaches and frameworks may improve wildlife–pathogen surveillance and our understanding of seemingly sporadic and rare pathogen outbreaks.

negative: Retinal pathology in multiple sclerosis: insight into the mechanisms of neuronal pathology

negative: Mathematical model of COVID-19 spread in Turkey and South Africa A comprehensive study about the spread of COVID-19 cases in Turkey and South Africa has been presented in this paper . An exhaustive statistical analysis encompassing arithmetic, geometric, harmonic means, standard deviation, skewness, variance, Pearson and Spearman correlation was derived from the data collected from Turkey and South Africa within the period of 11 March 2020 to 3 May 2020 and 05 March and 3 of May respectively. It was observed that in the case of Turkey, a negative Spearman correlation for the number of infected class and a positive Spearman correlation for both the number of deaths and recoveries were obtained. This implied that the daily infections could decrease, while the daily deaths and number of recovered people could increase under current conditions. In the case of South Africa, a negative Spearman correlation for both daily deaths and daily infected people was obtained, indicating that these numbers may decrease if the current conditions are maintained. The utilization of a statistical technique predicted the daily number of infected, recovered and dead people for each country; and three results were obtained for Turkey, namely an upper boundary, a prediction from current situation and lower boundary. The prediction shows that Turkey may register in the near future approximately more than 6000 new infections in a day as worst case scenario; and less than 300 cases in the perfect scenario. However, the country could register in the near future a daily number of 27000 people recovered from COVID-19 in the perfect scenario; and less than 5000 people in a worst scenario. Moreover, Turkey in a worst-case scenario could record a high number of approximately 200 deaths per day; and less than 150 deaths in a perfect scenario. Similarly, in the case of South Africa, the prediction results show that in the near future the country could register about 500 new infected cases daily and more than 25 deaths in the worst scenario; while in a perfect scenario less than 50 new infected and zero death cases could be recorded. The histograms of the daily number of newly infected, recovered and death showed a sign of lognormal and normal distribution, which is presented using the Bell curving method parameters estimation. A new mathematical model COVID-19 comprised of nine classes was suggested; of which a formula of the reproductive number, well-poseness of the solutions and the stability analysis were presented in details. The suggested model was further extended to the scope of nonlocal operators for each case; whereby the Atangana-Seda numerical method was used to provide numerical solutions, and simulations were performed for different non-integer numbers. Additionally, sections devoted to control optimal and others dedicated to compare cases between Turkey and South Africa with the aim to comprehend why there are less numbers of deaths and infected people in South Africa than Turkey were presented in details.

negative: Chapter 9 Environmental and Occupational Health Abstract Environmental and occupational health is affected by chemical, physical, radiological, and biological agents in the air, water, and soil. Health risks include injury, and exposure to toxic radiation, carcinogenic and teratogenic agents, leading to cancer, lung and heart diseases. Environmental factors may result in instant death or long-term illness from unsafe environmental or working conditions. The environment affects populations from small workplace settings to large-scale communities, as well as having global effects. International and governmental responsibility, through policies, laws, regulations, standards, policies, and planning, is vital for tackling global aspects of pollution, including climate change, cataclysmic natural events, drought, air and water pollution, and the potentially catastrophic effects of weather changes. Preparation for disasters is a core public health function in managing the after-effects of tsunamis, hurricanes, floods, and drought. These are potent political and public health issues with huge economic and societal effects.

negative: Lessons learned from the coronavirus health crisis in Madrid, Spain: How COVID-19 has changed our lives in the last two weeks

negative: Case- fatality rate in COVID- 19 patients: A meta-analysis of publicly accessible database A novel coronavirus was reported in Wuhan, China in December 2019 to cause severe acute respiratory symptoms (COVID- 19). In this meta-analysis, we estimated case fatality rate from COVID- 19 infection by random effect meta-analysis model with country level data. Publicly accessible web database WorldOMeter (https://www.worldometers.info/coronavirus/) was accessed on 24th March 2020 GMT and reported total number of cases, total death, active cases and seriously ill/ critically ill patients were retrieved. Primary outcome of this meta-analysis was case fatality rate defined by total number of deaths divided by total number of diagnosed cases. Pooled case fatality rate (95% CI) was 1.78 (1.34- 2.22) %. Between country heterogeneity was 0.018 (p<0.0001). Pooled estimate of composite poor outcome (95% CI) was 4.06 (3.24- 4.88) % at that point of time after exclusion of countries reported small number of cases. Pooled mortality rate (95% CI) was 33.97 (27.44- 40.49) % amongst closed cases (where patients have recovered or died) with. Meta regression analysis identified statistically significant association between health expenditure and mortality amongst closed cases (p=0.037).

negative: Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation Among Medical Students: A Systematic Review and Meta-Analysis. Importance Medical students are at high risk for depression and suicidal ideation. However, the prevalence estimates of these disorders vary between studies. Objective To estimate the prevalence of depression, depressive symptoms, and suicidal ideation in medical students. Data Sources and Study Selection Systematic search of EMBASE, ERIC, MEDLINE, psycARTICLES, and psycINFO without language restriction for studies on the prevalence of depression, depressive symptoms, or suicidal ideation in medical students published before September 17, 2016. Studies that were published in the peer-reviewed literature and used validated assessment methods were included. Data Extraction and Synthesis Information on study characteristics; prevalence of depression or depressive symptoms and suicidal ideation; and whether students who screened positive for depression sought treatment was extracted independently by 3 investigators. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Main Outcomes and Measures Point or period prevalence of depression, depressive symptoms, or suicidal ideation as assessed by validated questionnaire or structured interview. Results Depression or depressive symptom prevalence data were extracted from 167 cross-sectional studies (n = 116 628) and 16 longitudinal studies (n = 5728) from 43 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of depression or depressive symptoms was 27.2% (37 933/122 356 individuals; 95% CI, 24.7% to 29.9%, I2 = 98.9%). Summary prevalence estimates ranged across assessment modalities from 9.3% to 55.9%. Depressive symptom prevalence remained relatively constant over the period studied (baseline survey year range of 1982-2015; slope, 0.2% increase per year [95% CI, -0.2% to 0.7%]). In the 9 longitudinal studies that assessed depressive symptoms before and during medical school (n = 2432), the median absolute increase in symptoms was 13.5% (range, 0.6% to 35.3%). Prevalence estimates did not significantly differ between studies of only preclinical students and studies of only clinical students (23.7% [95% CI, 19.5% to 28.5%] vs 22.4% [95% CI, 17.6% to 28.2%]; P = .72). The percentage of medical students screening positive for depression who sought psychiatric treatment was 15.7% (110/954 individuals; 95% CI, 10.2% to 23.4%, I2 = 70.1%). Suicidal ideation prevalence data were extracted from 24 cross-sectional studies (n = 21 002) from 15 countries. All but 1 study used self-report instruments. The overall pooled crude prevalence of suicidal ideation was 11.1% (2043/21 002 individuals; 95% CI, 9.0% to 13.7%, I2 = 95.8%). Summary prevalence estimates ranged across assessment modalities from 7.4% to 24.2%. Conclusions and Relevance In this systematic review, the summary estimate of the prevalence of depression or depressive symptoms among medical students was 27.2% and that of suicidal ideation was 11.1%. Further research is needed to identify strategies for preventing and treating these disorders in this population.

negative: Comparison of different exit scenarios from the lock-down for COVID-19 epidemic in the UK and assessing uncertainty of the predictions We model further development of the COVID-19 epidemic in the UK given the current data and assuming different scenarios of handling the epidemic. In this research, we further extend the stochastic model suggested in \cite{us} and incorporate in it all available to us knowledge about parameters characterising the behaviour of the virus and the illness induced by it. The models we use are flexible, comprehensive, fast to run and allow us to incorporate the following: -time-dependent strategies of handling the epidemic; -spatial heterogeneity of the population and heterogeneity of development of epidemic in different areas; -special characteristics of particular groups of people, especially people with specific medical pre-histories and elderly. Standard epidemiological models such as SIR and many of its modifications are not flexible enough and hence are not precise enough in the studies that requires the use of the features above. Decision-makers get serious benefits from using better and more flexible models as they can avoid of nuanced lock-downs, better plan the exit strategy based on local population data, different stages of the epidemic in different areas, making specific recommendations to specific groups of people; all this resulting in a lesser impact on economy, improved forecasts of regional demand upon NHS allowing for intelligent resource allocation.

negative: No indications for overt innate immune suppression in critically ill COVID-19 patients At the end of March 2020, there were in excess of 800.000 confirmed cases of coronavirus disease 2019 (COVID-19) worldwide. Several reports suggest that, in severe cases, COVID-19 may cause a hyperinflammatory 'cytokine storm'. However, unlike SARS-CoV infection, high levels of anti-inflammatory mediators have also been reported in COVID-19 patients. One study reported that 16% of COVID-19 patients who died developed secondary infection, which might indicate an immune-suppressed state. We explored kinetics of mHLA-DR expression, the most widely used marker of innate immune suppression in critically ill patients, in COVID-19 patients admitted to the ICU. Twenty-four confirmed COVID-19 patients were included, of which 75% was male and 79% had comorbidities. All patients were mechanically ventilated and exhibited large high levels of inflammatory parameters such as CRP and PCT. mHLA-DR expression levels were mostly within the normal range of 15000 - 45000 mAb/cell and showed no change over time. COVID-19 patients displayed notably higher mHLA-DR expression levels compared with bacterial septic shock patients. None of the COVID-19 patients developed a secondary infection. In conclusion, despite a pronounced inflammatory response, mHLA-DR expression kinetics indicate no overt innate immune suppression in COVID-19 patients. These data signify that innate immune suppression as a negative feedback mechanism following PAMP-induced inflammation appears not to be present in COVID-19.

negative: Estimation of seroprevalence of novel coronavirus disease (COVID-19) using preserved serum at an outpatient setting in Kobe, Japan: A cross-sectional study. Summary Background Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been affecting many people on earth and our society. Japan is known to have relatively less number of infections as well as deaths among developed nations. However, accurate prevalence of COVID-19 in Japan remains unknown. Therefore, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection. Methods We conducted a cross-sectional serologic testing for SARS-CoV-2 antibody using 1,000 samples from patients at outpatient settings who visited the clinic from March 31 to April 7, 2020, stratified by decade of age and sex. Results There were 33 positive IgG among 1,000 serum samples (3.3%, 95%CI: 2.3-4.6%). By applying this figure to the census of Kobe City (poplation: 1,518,870), it is estimated that the number of people with positive IgG be 50,123 (95%CI: 34,934-69,868). Age and sex adjusted prevalence of positivity was 2.7% (95%CI 1.8-3.9%), and the estimated number of people with positive IgG was 40,999 (95%CI: 27,333-59,221). These numbers were 396 to 858 fold more than confirmed cases with PCR testing in Kobe City. Conclusions Our cross-sectional serological study suggests that the number of people with seropositive for SARS-CoV-2 infection in Kobe, Japan is far more than the confirmed cases by PCR testing.

negative: Potential impact of seasonal forcing on a SARS-CoV-2 pandemic A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.

negative: Paucity and disparity of publicly available sex-disaggregated data for the COVID-19 epidemic hamper evidence-based decision-making COVID-19 has joined the long list of human disorders with sexually dimorphic expression. Increased lethality in men was evident in the first large reports from ChinaCDC and WHO-China, and the gender gap appeared even wider in the early Italian outbreak. Newspapers and scientific journals alike have commented on this finding and the preexisting conditions, biological processes, and gender role behavior differences that may underlie it. However, as for other diseases, and in spite of years of advocating for the collection of raw epidemiological data and the analysis of clinical trial data sets by sex, very little appeared to be released about sex differences in characteristics of the epidemics beyond infection and death rates, such as severity of disease, comorbidities, rate of recovery, length of hospital stay, or number of tests for the SARS-CoV-2 coronavirus. These data are critical not only for scientists to understand the pathophysiology of disease, but also to inform decision-making by countries and healthcare systems on how to prioritize testing and best allocate scarce resources and relief funds. Systematic analysis of official websites for the 20 countries and 6 US states reporting the highest number of cases on March 21, 2020, revealed a wide disparity in sex-disaggregated data made available to the public and scholars. Only a handful of the countries reported cases by sex separately. None of the other characteristics, including fatality rates, were stratified by sex at the time. Beyond suboptimal sex disaggregation, our analysis found a paucity of usable raw data sets and a generalized lack of standardization of captured data, making comparisons difficult. A second round of data capture in April found more complete, but even more disparate, information. Our analysis revealed a wide range of sex ratios among confirmed cases, which changed over time. In countries where a male-biased sex ratio was initially reported, the reported proportion of women among cases dramatically increased in under 3 weeks. In contrast, men were consistently over-represented in severe cases, intensive care admissions, and deaths. We also show that the sex ratio varies with age, with a complex pattern, reproduced across the 6 countries for which data were found. Accurate, peer-reviewed, statistical analysis of harmonized, sex-disaggregated data for other characteristics of epidemics, such as availability of testing, suspected source of infection, or comorbidities will be critical to understand where the observed disparities come from and to generate evidence-based recommendations for decision-making by institutions and governments around the world.

negative: Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.

negative: Contact lens practice in the time of COVID-19

negative: Infectious Diseases among Refugee Children In recent years, there has been a substantial increase in refugee and asylum-seeking adults, adolescents and children to high-income countries. Infectious diseases remain the most frequently identified medical diagnosis among U.S.-bound refugee children. Medical screening and immunization are key strategies to reduce the risk of infectious diseases in refugee, internationally adopted, and immigrant children. Notable infectious diseases affecting refugee and other newly arriving migrants include latent or active tuberculosis, human immunodeficiency virus type 1 (HIV), hepatitis B, hepatitis C, vaccine-preventable diseases, malaria, and other parasitic infections. The U.S. Centers for Disease Control and Prevention and the American Academy of Pediatrics have published guidelines for health assessment of newly arriving immigrant, refugee, and internationally adopted children. Although, data on the health risks and needs of refugee exists in some high-income countries, there is an urgent need to develop robust evidence-informed guidance on screening for infectious diseases and vaccination strategies on a broader scale to inform national policies. Innovative approaches to reach migrant communities in the host nations, address health and other complex barriers to improve access to high-quality integrated health services, and strong advocacy to mobilize resources to improve health, safety, and wellbeing for refugee children and their families are urgent priorities.

negative: Coronavirus as a possible cause of severe acute respiratory syndrome Summary Background An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. Methods We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Findings Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. Interpretation A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

negative: Covid-19: Low skilled men have highest death rate of working age adults.

negative: The building of social resilience in Sichuan after the Wenchuan earthquake: A perspective of the socio-government interactions Abstract In November 2007, China implemented its Emergency Response Law to ensure national unified leadership and collaboration when responding to emergencies. In recent years, China’s main focuses for enhancing disaster management have included emergency preparation, emergency management, and legal system mechanisms. However, its well-designed management system faced a great challenge during the Wenchuan earthquake in 2008. By examining the literature on the development of disaster management, we realized that enhancing self-organization in communities can effectively resolve problems caused by collective actions and strengthen resilience to disasters. In the decade since the Wenchuan earthquake, the literature has focused more on empowering communities during disaster management in China. However, literature on the compatibility of social resilience and the government-dominant model in China is still scant. This study investigates China’s current disaster management system design; specifically, it identifies ways and methods for counteracting any conflicts between disaster management under social synergies and China’s emergency management system. It further explores what factors facilitate the balance between social synergies and the emergency management system if the two concepts were fused together. Using case studies, in-depth interviews, and a focus group in the field of public administration, this study collected qualitative data to understand the changes in China’s disaster management system since the Wenchuan earthquake as well as provide recommendations for future reform.

negative: Transmission Dynamics of COVID-19 and Impact on Public Health Policy In this work we construct a mathematical model for the transmission and spread of coronavirus disease 2019 or COVID-19. Our model features delay terms to account for (a) the time lapse or latency period between contracting the disease and displaying symptoms, and (b) the time lag in testing patients for the virus due to the limited numbers of testing facilities currently available. We find that the delay introduces a significant disparity between the actual and reported time-trajectories of cases in a particular region. Specifically, the reported case histories lag the actual histories by a few days. Hence, to minimize the spread of the disease, lockdowns and similarly drastic social isolation measures need to be imposed some time before the reported figures are approaching their peak values. We then account for the social reality that lockdowns can only be of a limited duration in view of practical considerations. We find that the most effective interval for imposing such a limited-time lockdown is one where the midpoint of the lockdown period coincides with the actual peak of the spread of the disease in the absence of the lockdown. We further show that the true effectivity of imposing a lockdown may be misrepresented and grossly underestimated by the reported case trajectories in the days following the action.

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: The Late Arrival of COVID-19 in Africa - Mitigating Pan-Continental Spread

negative: High COVID-19 incidence among Norwegian travellers returned from Lombardy: implications for travel restrictions On February 27th, three cases of COVID-19 were reported among Norwegians that had recently returned from Lombardy, Italy. Travellers from the region rapidly became the most common source of imported infections in the earliest stage of the Norwegian COVID-19 epidemic. The situation was exacerbated by the unfortunate temporal overlap between the Norwegian winter holidays and intense epidemic spread of COVID-19 in Northern Italy, resulting in a large number of infected travellers. Here we combined flight data on travels between Norway and Lombardy with patient-level data to determine the fraction of travellers returning to Norway that had been infected with SARS-CoV-2. Travellers returning to Norway from Lombardy contracted COVID-19 at incidence rates up to 0.02 per person-day in the period spanning February 21st and March 1st, with a clear uptick in transmission in the middle of the period. This shows an example of the infection risk in tourist destinations being several fold higher than elsewhere in the region. In Norway, this is also supported by high rates of infections among tourists returning from Austria in February and March, despite a low number of reported cases in the country at the time. The massive COVID-19 prevalence among travellers suggest that mandatory quarantine of returning travellers or suspension of non-essential international flights is essential if the aim is to control or suppress the COVID-19 pandemic.

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: A previously undescribed coronavirus associated with respiratory disease in humans. The etiology of acute respiratory tract illnesses is sometimes unclear due to limitations of diagnostic tests or the existence of as-yet-unidentified pathogens. Here we describe the identification and characterization of a not previously recognized coronavirus obtained from an 8-mo-old boy suffering from pneumonia. This coronavirus replicated efficiently in tertiary monkey kidney cells and Vero cells, in contrast to human coronaviruses (HCoV) 229E and OC43. The entire cDNA genome sequence of the previously undescribed coronavirus was determined, revealing that it is most closely related to porcine epidemic diarrhea virus and HCoV 229E. The maximum amino acid sequence identity between ORFs of the newly discovered coronavirus and related group 1 coronaviruses ranged from 43% to 67%. Real-time RT-PCR assays were designed to test for the prevalence of the previously undescribed coronavirus in humans. Using these tests, the virus was detected in four of 139 individuals (3%) who were suffering from respiratory illness with unknown etiology. All four patients suffered from fever, runny nose, and dry cough, and all four had underlying or additional morbidity. Our data will enable the development of diagnostic tests to study the prevalence and clinical impact of this virus in humans in more detail. Moreover, it will be important to discriminate this previously undescribed coronavirus from HCoV 229E and OC43 and the severe acute respiratory syndrome coronavirus.

negative: Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome The recent emergence of the Middle East respiratory syndrome (MERS)-CoV, a close relative of the Severe Acute respiratory syndrome (SARS)-CoV, both of which caused a lethal respiratory infection in humans, reinforces the need for further understanding of coronavirus pathogenesis and the host immune response. These viruses have evolved diverse strategies to evade and block host immune responses, facilitating infection and transmission. Pathogenesis following infection with these viruses is characterized by a marked delay in the induction of Type I interferon (IFN I) and, subsequently, by a poor adaptive immune response. Therapies that expedite IFN I induction as well as interventions that antagonize immunoevasive virus proteins are thus promising candidates for immune modulation.

negative: Die Anwendung der Traditionellen Chinesischen Medizin (TCM)/Akupunktur in der Therapie und Prävention von SARS-CoV-2-Infektionen: White Paper des Wissenschaftszentrums der deutschen Ärztegesellschaft für Akupunktur There are currently numerous suggestions on the potential effectiveness of traditional Chinese medicine (TCM)/acupuncture in the treatment of SARS-CoV‑2 infections and their associated symptoms. These reflections are based on molecular virology and clinical investigations resulting from the SARS epidemic in 2002/2003. The antiviral properties of Chinese herbal medicine (CHM) against SARS-CoV‑2 have not yet been investigated in depth. Clinical data relies on studies conducted prior to the corona pandemic. Current data is limited to a few internationally published case reports and observational studies published in China. There is a promising number of ongoing registered clinical trials. Evidence regarding TCM treatments other than CHM is poor. Based on the available data, a combination of Western and TCM approaches in the Western Hemisphere seems justified only if all conventional treatments are exhausted.

negative: SARS-CoV-2: virus dynamics and host response

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 synthesize 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 analyzed qualitative data using thematic synthesis. From the 218 identified articles, 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 who are those who had the illness and recovered, recognizing that some of these individuals will also be bereaved people. Previous pandemics appear to cause multiple losses both directly related to death itself and 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 postbereavement support.

negative: Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

negative: Mental health burden for the public affected by the COVID-19 outbreak in China: Who will be the high-risk group? In December, 2019, an outbreak of respiratory illness caused by Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread rapidly to other parts of China and around the world. We aimed to identify high-risk groups whose mental health conditions were vulnerable to the COVID-19 outbreak. Data were collected from 7,236 self-selected participants measured by anxiety symptoms, depressive symptoms, and sleep quality. The overall prevalence of anxiety symptoms, depressive symptoms, and poor sleep quality were 35.1%, 20.1%, and 18.2%, respectively. People aged < 35 years reported a higher prevalence of anxiety symptoms and depressive symptoms than people aged ≥ 35 years. Healthcare workers have the highest rate of poor sleep compared to other occupations. Healthcare workers/younger people who spent a high level of time (≥ 3 hours/day) had a particular higher prevalence of anxiety symptoms than in those who spent less time (< 1 hours/day and 1-2 hours/day) on the outbreak. During the COVID-19 outbreak, healthcare workers and younger people were at an especially high-risk of displaying psychological impact when they spent too much time thinking about the outbreak. Continuous monitoring of the psychological consequences for high-risk population should become routine as part of targeted interventions during times of crisis.I.

negative: Susceptibility to Upper Respiratory Tract Infection and Touching of the Eyes or Nose: A Cross‐sectional Study of Japanese Workers Susceptibility to Upper Respiratory Tract Infection and Touching of the Eyes or Nose: A Cross‐sectional Study of Japanese Workers: Yasushi FUKUNAKA, et al. Department of Safety and Health, Tokyo Gas Co., Ltd.— OBJECTIVES: This study was a cross‐sectional survey of Japanese workers regarding the relationship between touching the eyes or nose and susceptibility to URTI in workers. METHODS: The survey respondents were 4,663 Japanese workers. Subjects were surveyed via a self‐administered questionnaire regarding their susceptibility to URTI and how often they touched their eyes or nose. In addition, subjects were surveyed regarding their preventive behaviors and routine behaviors thought to be associated with URTIs. A multiple logistic regression model was used to assess the relationship between susceptibility to URTI and how often the eyes or nose are touched. RESULTS: Responses from 3,663 individuals who answered the self‐administered questionnaire were analyzed. There were 1,590 individuals (42.9%) with a “frequent incidence of URTIs”, defined as URTIs more than once a year. In terms of how often the eyes or nose are touched, the odds ratios (95% CI) for a frequent incidence of URTIs among the groups responding “sometimes” and “often” were 1.41 (1.21−1.63) and 1.96 (1.59−2.42) (trend test: p<0.001) compared with the groups responding “never” and “almost never”. Multivariate‐adjusted odds ratios adjusted for confounding factors, i.e., behaviors to prevent URTIs, routine behaviors associated with URTIs, age, sex and BMI, were 1.33 (1.14−1.54) and 1.69 (1.36−2.09) (trend test: p<0.001). CONCLUSIONS: The present cross‐sectional study indicates that susceptibility to URTI and how often the eyes or nose are touched are significantly associated in Japanese workers, independent of preventive behaviors and routine behaviors associated with URTIs.

negative: Alpha-1 adrenergic receptor antagonists for preventing acute respiratory distress syndrome and death from cytokine storm syndrome In severe viral pneumonias, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by a hyperinflammatory reaction ('cytokine storm syndrome') that leads to acute respiratory distress syndrome and death, despite maximal supportive care. Preventing hyperinflammation is key to avoiding these outcomes. We previously demonstrated that alpha-1 adrenergic receptor antagonists ($\alpha$-blockers) can prevent cytokine storm syndrome and death in mice. Here, we conduct a retrospective analysis of patients with acute respiratory distress or pneumonia (n = 13,125 and n = 108,956, respectively) from all causes; patients who were incidentally taking $\alpha$-blockers had a reduced risk of requiring ventilation (by 35% and 16%, respectively), and a reduced risk of being ventilated and dying (by 56% and 20%, respectively), compared to non-users. Beta-adrenergic receptor antagonists had no significant effects. These results highlight the urgent need for prospective trials testing whether prophylactic $\alpha$-blockers improve outcomes in diseases with a prominent hyperinflammatory component such as COVID-19.

negative: COVID 19 in INDIA: Strategies to combat from combination threat of life and livelihood Abstract INDIA- As for reported in 360 COVID-19 cases (till March 22, 2020), seven people were died, and 23 people were treated successfully.1 This virus can easily affect who having respiratory problem and especially who all have been aged older than sixty. Most of the affected peoples had reached India from different part of the world, as like of carrier. Owing to this, India made several precautionary measures to mitigate/neglect the disease in beginning stage, however, the denser population of country will not be simple to control the same for long time (community spread), if government will not incorporate the visionary strategies. Since attacked several nations have been worried mostly for their people life (health), despite that developing country like India with huge population should consider about the livelihood (for Below Poverty Line (BPL) people), equally with the life. This article will give insights to make effective strategy to culminate the world threat COVID-19 in India.

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: Evaluating the effect of public health intervention on the global-wide spread trajectory of Covid-19 As COVID-19 evolves rapidly, the issues the governments of affected countries facing are whether and when to take public health interventions and what levels of strictness of these interventions should be, as well as when the COVID-19 spread reaches the stopping point after interventions are taken. To help governments with policy-making, we developed modified auto-encoders (MAE) method to forecast spread trajectory of Covid-19 of countries affected, under different levels and timing of intervention strategies. Our analysis showed public health interventions should be executed as soon as possible. Delaying intervention 4 weeks after March 8, 2020 would cause the maximum number of cumulative cases of death increase from 7,174 to 133,608 and the ending points of the epidemic postponed from Jun 25 to Aug 22.

negative: Automatic X-ray COVID-19 Lung Image Classification System based on Multi-Level Thresholding and Support Vector Machine Abstract- The early detection of SARS-CoV-2, the causative agent of (COVID-19) is now a critical task for the clinical practitioners. The COVID-19 spread is announced as pandemic outbreak between people worldwide by WHO since 11/ March/ 2020. In this consequence, it is top critical priority to become aware of the infected people so that prevention procedures can be processed to minimize the COVID-19 spread and to begin early medical health care of those infected persons. In this paper, the deep studying based totally methodology is usually recommended for the detection of COVID-19 infected patients using X-ray images. The help vector gadget classifies the corona affected X-ray images from others through usage of the deep features. The technique is useful for the clinical practitioners for early detection of COVID-19 infected patients. The suggested system of multi-level thresholding plus SVM presented high accuracy in classification of the infected lung with Covid-19. All images were of the same size and stored in JPEG format with 512 * 512 pixels. The average sensitivity, specificity, and accuracy of the lung classification using the proposed model results were 95.76%, 99.7%, and 97.48%, respectively.

negative: Pause, Persist, Pivot: Key Decisions Health Professions Education Researchers Must Make About Conducting Studies During Extreme Events When extreme events occur, some research becomes a clear priority, but what becomes of all other research? Does it stop indefinitely, or can it be paused with plans to resume, persist with modifications, or pivot to address new priorities? Facing this dilemma and witnessing it among their fellow health professions education researchers, the authors recognized a need for guidance. This Invited Commentary presents a framework, organized as key questions related to the research stage and process, to assist health professions education researchers in making decisions about how to proceed with research that was planned or in progress when an extreme event occurred. Although at the time of this writing, the COVID-19 pandemic was the extreme event at hand, the authors intentionally created questions and discussed considerations that can be helpful for thinking through decisions in a variety of disruptions in health professions education research—many of which require similar difficult decisions and creative solutions to carry important research forward and maintain high quality.

negative: A Laboratory Risk Assessment during the Coronavirus (COVID-19) Pandemic

negative: MERS-CoV: transmisión y el papel de nuevas especies hospederas

negative: Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.

negative: Preparedness and Preventive Behaviors for a Pandemic Disaster Caused by COVID-19 in Serbia Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The disease was first detected in Wuhan, the capital of China’s Hubei province, in December 2019 and has since spread globally, especially to Europe and North America, resulting in the ongoing global coronavirus pandemic disaster of 2019–2020. Although most cases have mild symptoms, there is some progression to viral pneumonia and multi-organ failure and death. More than 4.6 million cases have been registered across 216 countries and territories as of 19 April 2020, resulting in more than 311,000 deaths. Risk to communities with continued widespread disease transmission depends on characteristics of the virus, including how well it spreads between people; the severity of resulting illness; and the medical or other measures available to control the impact of the virus (for example, vaccines or medications that can treat the illness) and the relative success of these. In the absence of vaccines or medications, non-pharmaceutical interventions were the most important response strategy based on community interventions such as person-to-person distancing, mask-wearing, isolation and good personal hygiene (hand-washing)—all of which have been demonstrated can reduce the impact of this seemingly unstoppable globally spreading natural disaster. This paper presents the results of quantitative research regarding the level of citizen preparedness for disasters caused by coronavirus disease (COVID-19) in Serbia. The survey was conducted using a questionnaire that was requested and then collected online among 975 respondents during disaster in April 2020. The questionnaire examined citizens’ basic socio-economic and demographic characteristics, their knowledge, preparedness, risk perception and preventive measures taken individually and as a community to prevent the death and widespread transmission of novel coronavirus disease 2019 in the Republic of Serbia. Based on the findings that there are major differences in the public’s perception of risks posed by communicable disease threats such as presented by COVID-19, emergency management agencies should use these differences to develop targeted strategies to enhance community and national preparedness by promoting behavioral change and improving risk management decision-making.

negative: Adjoint-based Data Assimilation of an Epidemiology Model for the Covid-19 Pandemic in 2020 Data assimilation is used to optimally fit a classical epidemiology model to the Johns Hopkins data of the Covid-19 pandemic. The optimisation is based on the confirmed cases and confirmed deaths. This is the only data available with reasonable accuracy. Infection and recovery rates can be infered from the model as well as the model parameters. The parameters can be linked with government actions or events like the end of the holiday season. Based on this numbers predictions for the future can be made and control targets specified. With other words: We look for a solution to a given model which fits the given data in an optimal sense. Having that solution, we have all parameters.

negative: Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung BACKGROUND: Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia. PA has the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier that Sphk2(−/−) mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group of Sphk2(−/−) and the wild type controls to better understand the underlying protective mechanisms related to the Sphk2 deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system. RESULTS: Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes following PA infection were identified using whole transcriptome of Sphk2(−/−) mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused by PA such as those involved in: 1. Immune response to PA infection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways. Our genomic data suggests a potential role for SPHK2 in PA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change. CONCLUSION: Using Sphk2(−/−) mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promoting PA pneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling in PA-induced lung inflammation could serve as a potential therapy to combat PA-induced pneumonia.

negative: Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.

negative: Fatal encephalitis associated with coronavirus OC43 in an immunocompromised child. A child with pre-B acute lymphoblastic leukaemia (ALL) developed fatal encephalitis associated with human coronavirus OC43 (HCoV-OC43). During chemotherapy the child had a persistent HCoV-OC43 respiratory infection and later developed progressive encephalitis. Cerebrospinal fluid was negative for pathogens including HCoV-OC43, but a brain biopsy was HCoV-OC43-positive by metagenomic next-generation sequencing.

negative: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.

negative: The computation of case fatality rate for novel coronavirus (COVID-19) based on Bayes theorem: An observational study BACKGROUND: When a new disease such starts to spread, the commonly asked questions are how deadly is it? and how many people are likely to die of this outbreak? The World Health Organization (WHO) announced in a press conference on January 29, 2020 that the death rate of COVID-19 was 2% on the case fatality rate (CFR). It was underestimated assuming no lag days from symptom onset to deaths while many CFR formulas have been proposed, the estimation on Bays theorem is worthy of interpretation. Hence, it is hypothesized that the over-loaded burdens of treating patients and capacities to contain the outbreak (LSBHRS) may increase the CFR. METHODS: We downloaded COVID-19 outbreak numbers from January 21 to February 14, 2020, in countries/regions on a daily basis from Github that contains information on confirmed cases in >30 Chinese locations and other countries/regions. The pros and cons were compared among the 5 formula of CFR, including [A] deaths/confirmed; [B] deaths/(deathsâ+ârecovered); [C] deaths/(cases x days ago); [D] Bayes estimation based on [A] and the outbreak (LSBHRS) in each country/region; and [E] Bayes estimation based on [C] deaths/(cases x days ago). The coefficients of variance (CVâ=âthe ratio of the standard deviation to the mean) were applied to measure the relative variability for each CFR. A dashboard was developed for daily display of the CFR across each region. RESULTS: The Bayes based on (A)[D] has the lowest CV (=0.10) followed by the deaths/confirmed (=0.11) [A], deaths/(deathsâ+ârecoveries) (=0.42) [B], Bayes based on (C) (=0.49) [E], and deaths/(cases x days ago) (=0.59) [C]. All final CFRs will be equal using the formula (from, A to E). A dashboard was developed for the daily reporting of the CFR. The CFR (3.7%) greater than the prior CFR of 2.2% was evident in LSBHRS, increasing the CFR. A dashboard was created to present the CFRs on COVID-19. CONCLUSION: We suggest examining both trends of the Bayes based on both deaths/(cases 7 days ago) and deaths/confirmed cases as a reference to the final CFR. An app developed for displaying the provisional CFR with the 2 CFR trends can improve the underestimated CFR reported by WHO and media.

negative: Cumulative general subject index volumes 1-30 Publisher Summary This chapter lists the important subjects that are discussed in the publication Studies in Natural Products Chemistry, Volumes 1–30, such as abdominal pain, acaricidal activities, acanthenes, gibberellins, glucoamylases, macarpine, and quercetin. The terms are mentioned along with the page numbers in which they are discussed in the publication.

negative: Upper airway symptoms in coronavirus disease 2019 (COVID-19)

negative: Unknown unknowns – COVID-19 and potential global mortality COVID-19 (SARS-CoV-2) is currently a global pandemic. This paper will attempt to estimate global infection rates and potential resultant mortality in the absence of effective treatment and/or vaccination. Calculations are based on World Health Organisation data from Wuhan in China: 14% of infected cases are severe, 5% require intensive care and 4% die. Estimated infection rates and mortality rates at the level of continents and some individual countries (when these are of sufficient size) are tabulated. This pandemic may cause close to half a billion deaths, i.e. 6% of the global population – and potentially more. At the risk of sounding sensational, but with a sober sense of realism, healthcare risks being plunged into the Middle-Ages if the public do not do their part. Infection cannot occur in the absence of contact. The only way to mitigate these numbers is to apply social distancing and take the standard precautions so frequently reiterated by Public Health: hand washing, avoid touching the face and so on. These measures are crucial as the human cost is going to be unthinkable even in the best-case scenarios that epidemiologists are modelling.

negative: The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis Background: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 vs. <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR=1.73, [95%CI 1.50-2.01]), hypertension (8 studies; 2.87 [2.09-3.93]), diabetes (9 studies; 3.20 [2.26-4.53]), and CVD (10 studies; 4.97 [3.76-6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Conclusions: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be used to inform objective decisions on COVID-19 testing, clinical management, and workforce planning.

negative: A cascade of causes that led to the COVID-19 tragedy in Italy and in other European Union countries

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

negative: CoroNet: A Deep Neural Network for Detection and Diagnosis of COVID-19 from Chest X-ray Images BACKGROUND AND OBJECTIVE: The novel Coronavirus also called COVID-19 originated in Wuhan, China in December 2019 and has now spread across the world. It has so far infected around 1.8 million people and claimed approximately 114698 lives overall. As the number of cases are rapidly increasing, most of the countries are facing shortage of testing kits and resources. The limited quantity of testing kits and increasing number of daily cases encouraged us to come up with a Deep Learning model that can aid radiologists and clinicians in detecting COVID-19 cases using chest X-rays. METHODS: In this study, we propose CoroNet, a Deep Convolutional Neural Network model to automatically detect COVID-19 infection from chest X-ray images. The proposed model is based on Xception architecture pre-trained on ImageNet dataset and trained end-to-end on a dataset prepared by collecting COVID-19 and other chest pneumonia X-ray images from two different publically available databases. RESULTS: CoroNet has been trained and tested on the prepared dataset and the experimental results show that our proposed model achieved an overall accuracy of 89.6%, and more importantly the precision and recall rate for COVID-19 cases are 93% and 98.2% for 4-class cases (COVID vs Pneumonia bacterial vs pneumonia viral vs normal). For 3-class classification (COVID vs Pneumonia vs normal), the proposed model produced a classification accuracy of 95%. The preliminary results of this study look promising which can be further improved as more training data becomes available. CONCLUSION: CoroNet achieved promising results on a small prepared dataset which indicates that given more data, the proposed model can achieve better results with minimum pre-processing of data. Overall, the proposed model substantially advances the current radiology based methodology and during COVID-19 pandemic, it can be very helpful tool for clinical practitioners and radiologists to aid them in diagnosis, quantification and follow-up of COVID-19 cases.

negative: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings BACKGROUND: Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. METHODS: Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. RESULTS: In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001). CONCLUSIONS: Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting.

negative: The RNA Virus Database http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.

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: Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0–54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m(2) (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m(2) and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

negative: Unmet Needs in Respiratory Diseases: “You Can’t Know Where You Are Going Until You Know Where You Have Been”—Anonymous The care of patients with respiratory diseases has improved vastly in the past 50 years. In spite of that, there are still massive challenges that have not been resolved. Although the incidence of tuberculosis has decreased in the developed world, it is still a significant public health problem in the rest of the world. There are still over 2 million deaths annually from tuberculosis, with most of these occurring in the developing world. Even with the development of new pharmaceuticals to treat tuberculosis, there is no indication that the disease will be eradicated. Respiratory syncytial virus, severe acute respiratory syndrome, and pertussis are other respiratory infectious diseases with special problems of their own, from vaccine development to vaccine coverage. Asthma, one of the most common chronic diseases in children, still accounts for significant mortality and morbidity, as well as high health care costs worldwide. Even in developed countries such as the USA, there are over 4,000 deaths per year. Severe asthma presents a special problem, but the question is whether there can be one treatment pathway for all patients with severe asthma. Severe asthma is a heterogeneous disease with many phenotypes and endotypes. The gene for cystic fibrosis was discovered over 24 years ago. The promise of gene therapy as a cure for the disease has fizzled out, and while new antimicrobials and other pharmaceuticals promise improved longevity and better quality of life, the average life span of a patient with cystic fibrosis is still at about 35 years. What are the prospects for gene therapy in the twenty-first century? Autoimmune diseases of the lung pose a different set of challenges, including the development of biomarkers to diagnose and monitor the disease and biological modulators to treat the disease.

negative: Generic probabilistic modelling and non-homogeneity issues for the UK epidemic of COVID-19 Coronavirus COVID-19 spreads through the population mostly based on social contact. To gauge the potential for widespread contagion, to cope with associated uncertainty and to inform its mitigation, more accurate and robust modelling is centrally important for policy making. We provide a flexible modelling approach that increases the accuracy with which insights can be made. We use this to analyse different scenarios relevant to the COVID-19 situation in the UK. We present a stochastic model that captures the inherently probabilistic nature of contagion between population members. The computational nature of our model means that spatial constraints (e.g., communities and regions), the susceptibility of different age groups and other factors such as medical pre-histories can be incorporated with ease. We analyse different possible scenarios of the COVID-19 situation in the UK. Our model is robust to small changes in the parameters and is flexible in being able to deal with different scenarios. This approach goes beyond the convention of representing the spread of an epidemic through a fixed cycle of susceptibility, infection and recovery (SIR). It is important to emphasise that standard SIR-type models, unlike our model, are not flexible enough and are also not stochastic and hence should be used with extreme caution. Our model allows both heterogeneity and inherent uncertainty to be incorporated. Due to the scarcity of verified data, we draw insights by calibrating our model using parameters from other relevant sources, including agreement on average (mean field) with parameters in SIR-based models.

negative: Outbreak of a new coronavirus: what anaesthetists should know

negative: The Framework for the Prediction of the Critical Turning Period for Outbreak of COVID-19 Spread in China based on the iSEIR Model The goal of this study is to establish a general framework for predicting the so-called critical Turning Period in an infectious disease epidemic such as the COVID-19 outbreak in China early this year. This framework enabled a timely prediction of the turning period when applied to Wuhan COVID-19 epidemic and informed the relevant authority for taking appropriate and timely actions to control the epidemic. It is expected to provide insightful information on turning period for the world's current battle against the COVID-19 pandemic. The underlying mathematical model in our framework is the individual Susceptible-Exposed- Infective-Removed (iSEIR) model, which is a set of differential equations extending the classic SEIR model. We used the observed daily cases of COVID-19 in Wuhan from February 6 to 10, 2020 as the input to the iSEIR model and were able to generate the trajectory of COVID-19 cases dynamics for the following days at midnight of February 10 based on the updated model, from which we predicted that the turning period of CIVID-19 outbreak in Wuhan would arrive within one week after February 14. This prediction turned to be timely and accurate, providing adequate time for the government, hospitals, essential industry sectors and services to meet peak demands and to prepare aftermath planning. Our study also supports the observed effectiveness on flatting the epidemic curve by decisively imposing the Lockdown and Isolation Control Program in Wuhan since January 23, 2020. The Wuhan experience provides an exemplary lesson for the whole world to learn in combating COVID-19.

negative: PEOPLE EXPERIENCING HOMELESSNESS: THEIR POTENTIAL EXPOSURE TO COVID-19 Abstract Background : Insufficient housing quality is associated with stress and mental health impacts. Crowding, pollution, noise, inadequate lighting, lack of access to green spaces, and other environmental factors associated with slums can exacerbate mental health disorders, including depression, anxiety, violence, and other forms of social dysfunction. Method : The studies were identified using large-sized newspapers with international circulation. Results : Experts say that people who sleep in shelters or on the streets already have lower life expectancy, suffer from addiction, and have underlying health conditions that put them at greater risk should they develop the virus. There are just so many competing and unmet needs, which makes it much harder for homeless to contend with all of this. If exposed, people experiencing homelessness might be more susceptible to illness or death due to the prevalence of underlying physical and mental medical conditions and a lack of reliable and affordable health care. Nevertheless, without an urgent solution, people experiencing homelessness will remain in limbo. Conclusions : Many people living on the streets already have a diminished health condition, higher rates of chronic illnesses or compromised immune systems, all of which are risk factors for developing a more serious manifestation of the coronavirus infection. Those suffering from mental illness may have difficulty in recognizing and responding to the threat of infection. Homeless people have less access to health care providers who could otherwise order diagnostic testing and, if confirmed, isolate them from others in coordination with local health departments.

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: 2019-nCoV - Towards a 4th generation vaccine The first report of the unusual manifestation of pneumonia-like symptoms in Wuhan City, China was made on 31 December 2019. Within one week, the Chinese authorities reported that they had identified the causative agent as a new member of the Coronavirus family, the same family of that was responsible for MERS and SARS not so many years ago. The new virus was called Novel Coronavirus 2019 (2019-nCoV). Three weeks later, the World Health Organization declared that 2019-nCoV was capable of direct human-to-human transmission, the virus had spread across several countries in three continents, and had infected close to two thousand people, of whom at least 1 in 5 quite severely. The number of fatalities was fast rising. Yet, the World Health Organization officially announced that there is still at present no recommended anti-nCoV vaccine for subject at-risk, nor treatment for patients with suspected or confirmed nCoV, let alone 2019-nCov. It is therefore timely and critical to propose new possible and practical approaches for preventive interventions for subjects at-risk, and for treatment of patients afflicted with 2019-nCov-induced disease (Corona Virus Disease 2019; COVID-19) before the present situation explodes into a worldwide pandemic. One such potential clinical protocol is proposed as a hypothesis.

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: Remission of Invasive, Cancer Stem-Like Glioblastoma Xenografts Using Lentiviral Vector-Mediated Suicide Gene Therapy BACKGROUND: Glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. The translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. Lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model. METHODOLOGY/PRINCIPAL FINDINGS: We used a rodent xenograft model that recapitulates the invasive and angiogenic features of human glioblastoma to analyze the transduction pattern and therapeutic efficacy of lentiviral pseudotyped vectors. Both, lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) and vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors very efficiently transduced human glioblastoma cells in vitro and in vivo. In contrast, pseudotyped gammaretroviral vectors, similar to those evaluated for clinical therapy of glioblastoma, showed inefficient gene transfer in vitro and in vivo. Both pseudotyped lentiviral vectors transduced cancer stem-like cells characterized by their CD133-, nestin- and SOX2-expression, the ability to form spheroids in neural stem cell medium and to express astrocytic and neuronal differentiation markers under serum conditions. In a therapeutic approach using the suicide gene herpes simplex virus thymidine kinase (HSV-1-tk) fused to eGFP, both lentiviral vectors mediated a complete remission of solid tumors as seen on MRI resulting in a highly significant survival benefit (p<0.001) compared to control groups. In all recurrent tumors, surviving eGFP-positive tumor cells were found, advocating prodrug application for several cycles to even enhance and prolong the therapeutic effect. CONCLUSIONS/SIGNIFICANCE: In conclusion, lentiviral pseudotyped vectors are promising candidates for gene therapy of glioma in patients. The inefficient gene delivery by gammaretroviral vectors is in line with the results obtained in clinical therapy for GBM and thus confirms the high reproducibility of the invasive glioma animal model for translational research.

negative: Internet Search Patterns Reveal Clinical Course of Disease Progression for COVID-19 and Predict Pandemic Spread in 32 Countries Effective public health response to COVID-19 relies on accurate and timely surveillance of local pandemic spread, as well as rapid characterization of the clinical course of disease in affected individuals. De novo diagnostic testing methods developed for emergent pandemics are subject to significant development delays and capacity limitations. There is a critical need for complementary surveillance approaches that can function at population-scale to inform public health decisions in real-time. Internet search patterns provide a number of important advantages relative to laboratory testing. We conducted a detailed global study of Internet search patterns related to COVID-19 symptoms in multiple languages across 32 countries on six continents. We found that Internet search patterns reveal a robust temporal pattern of disease progression for COVID-19: Initial symptoms of fever, dry cough, sore throat and chills are followed by shortness of breath an average of 5.22 days [95% CI 3.30-7.14] after symptom onset, matching the precise clinical course reported in the medical literature. Furthermore, we found that increases in COVID-19-symptom-related searches predict increases in reported COVID-19 cases and deaths 18.53 days [95% CI 15.98-21.08] and 22.16 days [95% CI 20.33-23.99] in advance, respectively. This is the first study to show that Internet search patterns can be used to reveal the detailed clinical course of a disease. These data can be used to track and predict the local spread of COVID-19 before widespread laboratory testing becomes available in each country, helping to guide the current public health response.

negative: COVID-19 Pneumonia in Asymptomatic Trauma Patients; Report of 8 Cases We are currently involved in the novel coronavirus 2019 (COVID-19) pandemic. A considerable number of COVID-19 infected cases are asymptomatic but they can transmit the disease to others, especially healthcare workers. In this study, we reported 8 incidentally detected cases of COVID-19 pneumonia in chest computed tomography (CT) scan of patients referred to emergency department following multiple trauma without any respiratory symptoms.

negative: Coronavirus disease: challenges for psychiatry Coronavirus disease (COVID-19) presents two urgent health problems: the illness caused by the virus itself and the anxiety, panic and psychological problems associated with the pandemic. Both problems present substantial challenges for our patients, their families, our multidisciplinary teams and our psychiatrist colleagues. We need good psychiatry, now more than ever.

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: Media's effect on shaping knowledge, awareness risk perceptions and communication practices of pandemic COVID-19 among pharmacists Abstract Background Coronavirus disease (COVID-19), an infection of the zoonotic coronavirus, is presenting a healthcare challenge around the globe. This study aims to assess the levels of disease knowledge and risk perception among pharmacists. We also recognize predictors of risk perception and perceived media roles. Methods This is a questionnaire-base cross-sectional study. The questionnaire was developed on a web-based platform and invitations were sent to pharmacists nationwide to participate in the study using social media applications. Results A total of 486 pharmacists participated in this study, where females were dominant (78.6%, n = 382). Most (40.4%, n = 198) pharmacists scored 4 out of 5 in basic disease knowledge, and more than half were able to recognize common methods of spread. Risk was highly perceived among participants, and was predicted by gender, living area, and having children (p < 0,05). Frequency of watching the media and sources of information also influenced both risk perception and perceived media roles. Conclusion Disease awareness among pharmacists, as well as risk perception must be considered for effective risk communication planning. The role of media in shaping perceptions should also be carefully studied to encourage compliance with government containment measures and engagement in preventive behaviors.

negative: Severe Infections in the Returning Traveler The ease of air travel has made spread of infectious agents a global problem. There are a multitude of tropical diseases ranging from benign viral illnesses to highly contagious and life-threatening diseases and it is important to take a detailed clinical and travel history from the ill returning traveller, especially in the fi rst 4 weeks of return.

negative: Generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies Indoor air can be an important vehicle for a variety of human pathogens. This review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. The following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (Aspergillus, Penicillium, and Cladosporium spp and Stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (Clostridium difficile and Bacillus anthracis). An overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. Available guidelines from the U.S. Environmental Protection Agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. Recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. Furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed.

negative: Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study Abstract Background: The clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. Methods: In this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients' electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020. Findings: 291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p<0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15). Interpretation: The epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.

negative: Human coronavirus NL63, a new respiratory virus From the mid-1960s onwards, it was believed that only two human coronavirus species infect humans: HCoV-229E and HCoV-OC43. Then, in 2003, a novel member of the coronavirus family was introduced into the human population: SARS-CoV, causing an aggressive lung disease. Fortunately, this virus was soon expelled from the human population, but it quickly became clear that the human coronavirus group contains more members then previously assumed, with HCoV-NL63 identified in 2004. Despite its recent discovery, ample results from HCoV-NL63 research have been described. We present an overview of the publications on this novel coronavirus.

negative: Recommendations on cardiopulmonary resuscitation strategy and procedure for novel coronavirus pneumonia

negative: The phenotypic changes of Î³Î´ T cells in COVID-19 patients A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which caused by SARS-CoV-2 and broken in Wuhan, China in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. Also, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in {gamma}{delta} T cells. In comparison to HD, the {gamma}{delta} T cells percentage was decreased. {gamma}{delta} T cells are able to immediately respond to SARS-CoV-2 infection and upregulate the activation marker CD25. In addition, the increased expression of CD4 in {gamma}{delta} T cells may serve as a biomarker for the assessment of SARS-CoV-2 infection.

negative: The Coronavirus Pandemic: "The Show Must Not Go On"

negative: The SARS-CoV-2 outbreak: What we know Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

negative: COVID-19: Challenges to GIS with Big Data Abstract The outbreak of the 2019 novel coronavirus disease (COVID-19) has caused more than 100,000 people infected and thousands of deaths. Currently, the number of infections and deaths is still increasing rapidly. COVID-19 seriously threatens human health, production, life, social functioning and international relations. In the fight against COVID-19, Geographic Information Systems (GIS) and big data technologies have played an important role in many aspects, including the rapid aggregation of multi-source big data, rapid visualization of epidemic information, spatial tracking of confirmed cases, prediction of regional transmission, spatial segmentation of the epidemic risk and prevention level, balancing and management of the supply and demand of material resources, and social-emotional guidance and panic elimination, which provided solid spatial information support for decision-making, measures formulation, and effectiveness assessment of COVID-19 prevention and control. GIS has developed and matured relatively quickly and has a complete technological route for data preparation, platform construction, model construction, and map production. However, for the struggle against the widespread epidemic, the main challenge is finding strategies to adjust traditional technical methods and improve speed and accuracy of information provision for social management. At the data level, in the era of big data, data no longer come mainly from the government but are gathered from more diverse enterprises. As a result, the use of GIS faces difficulties in data acquisition and the integration of heterogeneous data, which requires governments, businesses, and academic institutions to jointly promote the formulation of relevant policies. At the technical level, spatial analysis methods for big data are in the ascendancy. Currently and for a long time in the future, the development of GIS should be strengthened to form a data-driven system for rapid knowledge acquisition, which signifies that GIS should be used to reinforce the social operation parameterization of models and methods, especially when providing support for social management.

negative: Statistical Explorations and Univariate Timeseries Analysis on COVID-19 Datasets to Understand the Trend of Disease Spreading and Death “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, the novel coronavirus, is responsible for the ongoing worldwide pandemic. “World Health Organization (WHO)” assigned an “International Classification of Diseases (ICD)” code—“COVID-19”-as the name of the new disease. Coronaviruses are generally transferred by people and many diverse species of animals, including birds and mammals such as cattle, camels, cats, and bats. Infrequently, the coronavirus can be transferred from animals to humans, and then propagate among people, such as with “Middle East Respiratory Syndrome (MERS-CoV)”, “Severe Acute Respiratory Syndrome (SARS-CoV)”, and now with this new virus, namely “SARS-CoV-2”, or human coronavirus. Its rapid spreading has sent billions of people into lockdown as health services struggle to cope up. The COVID-19 outbreak comes along with an exponential growth of new infections, as well as a growing death count. A major goal to limit the further exponential spreading is to slow down the transmission rate, which is denoted by a “spread factor (f)”, and we proposed an algorithm in this study for analyzing the same. This paper addresses the potential of data science to assess the risk factors correlated with COVID-19, after analyzing existing datasets available in “ourworldindata.org (Oxford University database)”, and newly simulated datasets, following the analysis of different univariate “Long Short Term Memory (LSTM)” models for forecasting new cases and resulting deaths. The result shows that vanilla, stacked, and bidirectional LSTM models outperformed multilayer LSTM models. Besides, we discuss the findings related to the statistical analysis on simulated datasets. For correlation analysis, we included features, such as external temperature, rainfall, sunshine, population, infected cases, death, country, population, area, and population density of the past three months—January, February, and March in 2020. For univariate timeseries forecasting using LSTM, we used datasets from 1 January 2020, to 22 April 2020.

negative: COVID-19 outbreak: Migration, effects on society, global environment and prevention Abstract The COVID-19 pandemic is considered as the most crucial global health calamity of the century and the greatest challenge that the humankind faced since the 2nd World War. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China and was named by the World Health Organization as COVID-19 (coronavirus disease 2019). A new class of corona virus, known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been found to be responsible for occurrence of this disease. As far as the history of human civilization is concerned there are instances of severe outbreaks of diseases caused by a number of viruses. According to the report of the World Health Organization (WHO as of April 18 2020), the current outbreak of COVID-19, has affected over 2164111 people and killed more than 146,198 people in more than 200 countries throughout the world. Till now there is no report of any clinically approved antiviral drugs or vaccines that are effective against COVID-19. It has rapidly spread around the world, posing enormous health, economic, environmental and social challenges to the entire human population. The coronavirus outbreak is severely disrupting the global economy. Almost all the nations are struggling to slow down the transmission of the disease by testing & treating patients, quarantining suspected persons through contact tracing, restricting large gatherings, maintaining complete or partial lock down etc. This paper describes the impact of COVID-19 on society and global environment, and the possible ways in which the disease can be controlled has also been discussed therein.

negative: Clinical Characteristics of Hospitalized Patients with SARS-CoV-2 and Hepatitis B virus Co-infection Background & Aims The coronavirus disease 2019 (COIVD-19) caused by SARS-CoV-2 has been characterized as a pandemic, which causes a serious public health challenge in the world. A very large group of patients infected by HBV has been reported worldwide, especially in China. In order to answer whether specific treatment strategy on the patients coinfected with HBV and SARS-CoV-2, it requires profound understanding of the clinical characteristics on those patients. However, the impacts of SARS-CoV-2 infection on HBV patients remain largely unknown. Approach & Results In this retrospective investigation, we included 123 COVID-19 patients admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from January 5 to March 7, 2020. All enrolled patients are the laboratory confirmed COVID-19 pneumonia cases according to the criteria reported previously. A total of 123 patients were analyzed for their Clinical records, laboratory results including the diagnosis of HBV infection and liver function. Among 123 confirmed COVID-19 patients, the mean age was 51 years old and 59.3% were females (73/123). Fifteen were previously HBV infected patients, 66.7% of them were males (10/15), patients with HBV infection appeared to have a higher incidence of liver cirrhosis and an increased level of total bilirubin. Seven (46.7%) patients with HBV infection were defined as severe cases, while the severity rate was 24.1% for the patients without HBV infection (26/108). The mortality of patients with HBV infection was 13.3% (2/15) compared to 2.8% (3/108) for the patients without HBV infection. Conclusions SARS-CoV-2 infection may cause liver function damage in COVID-19 cases and the patients with HBV infection are likely to have more severe disease outcome.

negative: Relationship between the ABO Blood Group and the COVID-19 Susceptibility The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.

negative: Dual roles of calpain in facilitating Coxsackievirus B3 replication and prompting inflammation in acute myocarditis Abstract Background Viral myocarditis (VMC) treatment has long been lacking of effective methods. Our former studies indicated roles of calpain in VMC pathogenesis. This study aimed at verifying the potential of calpain in Coxsackievirus B3 (CVB3)-induced myocarditis treatment. Methods A transgenic mouse overexpressing the endogenous calpain inhibitor, calpastatin, was introduced in the study. VMC mouse model was established via intraperitoneal injection of CVB3 in transgenic and wild mouse respectively. Myocardial injury was assayed histologically (HE staining and pathology grading) and serologically (myocardial damage markers of CK-MB and cTnI). CVB3 replication was observed in vivo and in vitro via the capsid protein VP1 detection or virus titration. Inflammation/fibrotic factors of MPO, perforin, IFNγ, IL17, Smad3 and MMP2 were evaluated using western blot or immunohistology stain. Role of calpain in regulating fibroblast migration was studied in scratch assays. Results Calpastatin overexpression ameliorated myocardial injury induced by CVB3 infection significantly in transgenic mouse indicated by reduced peripheral CK-MB and cTnI levels and improved histology injury. Comparing with CVB3-infected wild type mouse, the transgenic mouse heart tissue carried lower virus load. The inflammation factors of MPO, perforin, IFNγ and IL17 were down-regulated accompanied with fibrotic agents of Smad3 and MMP2 inhibition. And calpain participated in the migration of fibroblasts in vitro, which further proves its role in regulating fibrosis. Conclusion Calpain plays dual roles of facilitating CVB3 replication and inflammation promotion. Calpain inhibition in CVB3-induced myocarditis showed significant treatment effect. Calpain might be a novel target for VMC treatment in clinical practices.

negative: Conservation of polyamine regulation by translational frameshifting from yeast to mammals Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficiency of the frameshift event reflects cellular polyamine levels creating the autoregulatory feedback loop. As shown here, the yeast antizyme gene and several newly identified antizyme genes from different nematodes also require a ribosomal frameshift event for their expression. Twelve nucleotides around the frameshift site are identical between S.pombe and the mammalian counterparts. The core element for this frameshifting is likely to have been present in the last common ancestor of yeast, nematodes and mammals.

negative: A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease‐19 (COVID‐19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID‐19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID‐19.

negative: How the world's collective attention is being paid to a pandemic: COVID-19 related 1-gram time series for 24 languages on Twitter In confronting the global spread of the coronavirus disease COVID-19 pandemic we must have coordinated medical, operational, and political responses. In all efforts, data is crucial. Fundamentally, and in the possible absence of a vaccine for 12 to 18 months, we need universal, well-documented testing for both the presence of the disease as well as confirmed recovery through serological tests for antibodies, and we need to track major socioeconomic indices. But we also need auxiliary data of all kinds, including data related to how populations are talking about the unfolding pandemic through news and stories. To in part help on the social media side, we curate a set of 1000 day-scale time series of 1-grams across 24 languages on Twitter that are most `important' for March 2020 with respect to March 2019. We determine importance through our allotaxonometric instrument, rank-turbulence divergence. We make some basic observations about some of the time series, including a comparison to numbers of confirmed deaths due to COVID-19 over time. We broadly observe across all languages a peak for the language-specific word for `virus' in January followed by a decline through February and a recent surge through March. The world's collective attention dropped away while the virus spread out from China. We host the time series on Gitlab, updating them on a daily basis while relevant. Our main intent is for other researchers to use these time series to enhance whatever analyses that may be of use during the pandemic as well as for retrospective investigations.

negative: On the death of 100 + Italian doctors from COVID-19

negative: World governments should protect their population from COVID-19 pandemic using Italy and Lombardy as precursor The COVID-19 pandemic is spreading worldwide. Italy emerged early on as the country with the largest outbreak outside Asia. The outbreak in Northern Italy demonstrates that it is fundamental to contain the virus' spread at a very early stage of diffusion. At later stages, no containment measure, even if strict, can prevent the saturation of the hospitals and of the intensive care units in any country. Here we show that it is possible to predict when the intensive care units will saturate, within a few days from the first cases of COVID-19 intensive care patients. Using early counts of intensive care patients, we predict the saturation for Lombardy, Italy. Governments should use the Italian precursor to control the outbreak of COVID-19 and prevent the saturation of their intensive care units to protect their population.

negative: Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein BACKGROUND Nucleic acid test and antibody assay have been employed in the diagnosis for SARS-CoV-2 infection, but the use of viral antigen for diagnosis has not been successfully developed. Theoretically, viral antigen is the specific marker of the virus and precedes antibody appearance within the infected population. There is a clear need of detection of viral antigen for rapid and early diagnosis. METHODS We included a cohort of 239 participants with suspected SARS-CoV-2 infection from 7 centers for the study. We measured nucleocapsid protein in nasopharyngeal swab samples in parallel with the nucleic acid test. Nucleic acid test was taken as the reference standard, and statistical evaluation was taken in blind. We detected nucleocapsid protein in 20 urine samples in another center, employing nasopharyngeal swab nucleic acid test as reference standard. RESULTS We developed a fluorescence immunochromatographic assay for detecting nucleocapsid protein of SARS-CoV-2 in nasopharyngeal swab sample and urine within 10 minutes. 100% of nucleocapsid protein positive and negative participants accord with nucleic acid test for same samples. Further, earliest participant after 3 days of fever can be identified by the method. In an additional preliminary study, we detected nucleocapsid protein in urine in 73.6% of diagnosed COVID-19 patients. CONCLUSIONS Those findings indicate that nucleocapsid protein assay is an accurate, rapid, early and simple method for diagnosis of COVID-19. Appearance of nucleocapsid protein in urine coincides our finding of the SARS-CoV-2 invading kidney and might be of diagnostic value.

negative: Will novel virus go pandemic or be contained?

negative: Disease Transmission and Networks ☆ Abstract While epidemiological models have traditionally assumed that diseases spread by the mass action principle, actual contact networks within social groups do not meet this assumption. Theoretical models have shown that disease dynamics could vary considerably under different types of contact networks, but these models face challenges in terms of their evaluation due to the difficulty of collecting empirical data. The honeybee colony with its elaborate social organization and large repertoire of diseases provides an ideal setting to explore how the structure of the contact network contributes to the transmission of a disease.

negative: The time-series ages distribution of the reported COVID-2019 infected people suggests the undetected local spreading of COVID-2019 in Hubei and Guangdong provinces before 19th Jan 2020 COVID-2019 is broken out in China. It becomes a severe public health disaster in one month. Find the period in which the spreading of COVID-2019 was overlooked, and understand the epidemiological characteristics of COVID-2019 in the period will provide valuable information for the countries facing the threats of COVID-2019. The most extensive epidemiological analysis of COVID-2019 shows that older people have lower infection rates compared to middle-aged persons. Common sense is that older people prefer to report their illness and get treatment from the hospital compared to middle-aged persons. We propose a hypothesis that when the spreading of COVID-2019 was overlooked, we will find more older cases than the middle-aged cases. At first, we tested the hypothesis with 4597 COVID-2019 infected samples reported from 26th Nov 2019 to 17th Feb 2020 across the mainland of China. We found that 19th Jan 2020 is a critical time point. Few samples were reported before that day, and most of them were older ones. Then samples were explosively increased after that day, and many of them were middle-aged people. We have demonstrated the hypothesis to this step. Then, we grouped samples by their residences(provinces). We found that, in the provinces of Hubei and Guangdong, the ages of samples reported before 19th Jan 2020 are significantly higher than the ages of samples reported after that day. It suggests the COVID-2019 may be spreading in Hubei and Guangdong provinces before 19th Jan 2020 while people were unconscious of it. At last, we proposed that the ages distribution of each-day-reported samples could serve as a warning indicator of whether all potential COVID-2019 infected people are found. We think the power of our analysis is limit because 1. the work is data-driven, and 2. only ~5% of the COVID-2019 infected people in China are included in the study. However, we believe it still shows some value for its ability to estimate the possible unfound COVID-2019 infected people.

negative: Impacts of Early Interventions on the Age-Specific Incidence of COVID-19 in New York, Los Angeles, Daegu and Nairobi Background COVID-19 has caused an unprecedented public health crisis and economic shock to the global economy. While many countries were affected, regions with an older population and weaker public health interventions tended to suffer more morbidity and mortality. Here we model and quantify the age-specific incidence of COVID-19 in four pandemic cities under different interventions. Methods We developed an age-specific and multiple-stage susceptible-exposed-infected-recovered-hospitalized-quarantined-dead (SEIR-HQD) dynamical systems model expanded from the more basic SEIR model by incorporating location- and age-specific contact matrices to estimate the outcomes of COVID-19. Utilizing latest estimates of epidemiological parameters and demographic data, we model the potential effects of various interventions in four representative cities with different population structures - New York, Los Angeles, Daegu and Nairobi. We compared the effects of different interventions in the age-structure populations specific to each city. These policy options are then applied to determine the potential for effective containment. We model these dynamic policy scenarios to assess the risks of less-stringent social distancing, as has been proposed by those arguing to enhance economic activity over public health and safety. Finally, we explored the health impacts of different policy action timelines to understand the benefits of early interventions. Findings We find the spread of COVID-19 to be dramatically different in the regions modeled, with the primary drivers the variation of population age structures, and the dynamics of interactions of the younger demographics, whose higher interaction rates can lead to increasing transmission rates across these communities. A city with younger citizens may also have fewer hospitalized cases and deaths. Our modeling quantifies the value of early interventions, which avoided an additional 5%, 16%, 37% and 43% of the infections in Daegu, Nairobi, New York and Los Angeles, respectively, compared to what has been observed in the four cities. The finding is clear: in the absence of pharmaceutical options, delaying strict social policy interventions has resulted in substantial public health cost. This modeling can, and will, be applied to other cities and regions, and conducted in conjunction with other health insults, such as exposure to air pollution. Critically, we find that school closures, working from home, and reduction in other mobility were most beneficial for younger population (0-19 years old), middle-age (20-59 years old) population and older population (60 years and older), respectively across each city. Specifically, school closure avoided 25%, 18%, 16% and 12% of the infections for the population under 20 years old in Daegu, Los Angeles, New York and Nairobi, respectively. A 50% and 80% population working from home policy avoids 8% and 15% of the infections. Reduction in mobility was more effective than the working from home strategy. Any single social distancing policy if enacted alone can delay the spread of COVID-19 but was unable to totally suppress the infection. Coordinated policy action can be highly effective. Increasing the quarantine rate to 10% of infectious cases was more effective than strict social distancing alone in this study, although together they can suppress 80% of the epidemic. A combination of moderate social distancing and quarantine strategies was able to avoid 99% of the infections. Interpretation Moderate social distancing together with high quarantine rates was effective in each of the four cities. COVID-19 caused more deaths and hospitalization in cities with an ageing population than those with a younger population. However, in the cities with a younger population, there is a clear need to implement a social distancing strategy that is even more strict due to the higher transmission rates among younger people. Cities with more older people should prepare more hospital beds and healthcare facilities to save people who are in critical conditions. Cities with ageing population should take targeted action for the elderly to avoid the severe impacts on the vulnerable populations. Increasing quarantine rate is an effective strategy to avoid the substantial infection while also does not influence the economy fiercely. We recommend countries or regions experiencing, or likely to experience the rapid spread of COVID-19, to implement combination of multiple strategies in the early stage of the breakout which can avoid over 90% of infected cases.

negative: Coronavirus disease 2019 (COVID-19) outbreak in Iran: Actions and problems

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: The Impact of Population Growth on the Epidemiology and Evolution of Infectious Diseases It is generally expected that in developing countries the epidemiological transition, with improved health and lower mortality rates, will eventually lead to a demographic transition with lower fertility rates. The reductions in mortality characterising the epidemiological transition are often associated with controlling the infectious diseases within populations, which leaves the chronic diseases associated with old age, cancer and heart disease dominating the causes of death. However, if the demographic transition does not occur quickly, populations can grow rapidly, creating an increased potential for spread of infectious disease. These infectious diseases could, in turn, increase death rates amongst young people and reverse the epidemiological transition. The relationship between population growth, size and infection depends upon the changes in contact pattern associated with there being more people. If facilities can keep pace with growth, then the increase in contact rates can be kept to a minimum, and the potential reversal in the epidemic transition prevented. This makes development a crucial adjunct to population growth if the global community is not to be increasingly exposed to pandemics of infectious disease. Here we review the epidemiological and demographic theory which relates population growth and infectious disease.

negative: COVID-19 and diabetes: Can DPP4 inhibition play a role?

negative: D(2)EA: Depict the Epidemic Picture of COVID-19 The outbreak of coronavirus disease 2019 (COVID-19) has aroused a global alert. To release social panic and guide future schedules, this article proposes a novel mathematical model, the Delay Differential Epidemic Analyzer (D(2)EA), to analyze the dynamics of epidemic and forecast its future trends. Based on the traditional Susceptible-Exposed-Infectious-Recovered (SEIR) model, the D(2)EA model innovatively introduces a set of quarantine states and applies both ordinary differential equations and delay differential equations to describe the transition between two states. Potential variations of practical factors are further considered to reveal the true epidemic picture. In the experiment part, we use the D(2)EA model to simulate the epidemic in Hubei Province. Fitting to the collected real data as non-linear optimization, the D(2)EA model forecasts that the accumulated confirmed infected cases in Hubei Province will reach the peak at the end of February and then steady down. We also evaluate the effectiveness of the quarantine measures and schedule the date to reopen Hubei Province.

negative: Site-specific analysis of the SARS-CoV-2 glycan shield The emergence of the betacoronavirus, SARS-CoV-2 that causes COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, that mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in immune evasion and occluding immunogenic protein epitopes. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

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: On predicting the novel COVID-19 human infections by using Infectious Disease modelling method in the Indian State of Tamil Nadu during 2020 Since the introduction of the novel Corona Virus (The COVID 19) to the Chinese city Wuhan in the Hubei province during the late December 2019, the effectiveness of the deadly disease, its human infection, spreading severity and the mortality rate of the infection has been an issue of debate. The outbreak of the virus along the time has become a massive threat to the global public health security and has been declared as a pandemic. Accounting the radical number of increases in the infected cases and the death due to COVID 19 infections around the globe, there is a need to predict the infections among the people by making proper optimization and using various Infectious Disease modelling (IDM) methods, in order to challenge the outcome. In comparison with previous diseases like SARS and Ebola viruses, the new corona virus (COVID 19) infections are infectious during the incubation period. In addition to that, naturally produced droplets from humans (e.g. droplets produced by breathing, talking, sneezing, coughing) and Person-to-person contact transmission are reported to be the foremost ways of transmission of novel corona virus. By considering the above two factors, a modified SEIR (Susceptibility Exposure Infection Recovery) method have been used for predicting the spread of the infections in the state of Tamil Nadu which is located in the southern part of India. Further, we have utilized the current surveillance data from Health and Family Welfare Department, Government of Tamil Nadu to accurately predict the spreading trend of the infection on a state level.

negative: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19.

negative: Window of Opportunity for Mitigation to Prevent Overflow of ICU capacity in Chicago by COVID-19 We estimate the growth in demand for ICU beds in Chicago during the emerging COVID-19 epidemic, using state-of-the-art computer simulations calibrated for the SARS-CoV-2 virus. The questions we address are these: (1) Will the ICU capacity in Chicago be exceeded, and if so by how much? (2) Can strong mitigation strategies, such as lockdown or shelter in place order, prevent the overflow of capacity? (3) When should such strategies be implemented? Our answers are as follows: (1) The ICU capacity may be exceeded by a large amount, probably by a factor of ten. (2) Strong mitigation can avert this emergency situation potentially, but even that will not work if implemented too late. (3) If the strong mitigation precedes April 1st, then the growth of COVID-19 can be controlled and the ICU capacity could be adequate. The earlier the strong mitigation is implemented, the greater the probability that it will be successful. After around April 1 2020, any strong mitigation will not avert the emergency situation. In Italy, the lockdown occurred too late and the number of deaths is still doubling every 2.3 days. It is difficult to be sure about the precise dates for this window of opportunity, due to the inherent uncertainties in computer simulation. But there is high confidence in the main conclusion that it exists and will soon be closed. Our conclusion is that, being fully cognizant of the societal trade-offs, there is a rapidly closing window of opportunity to avert a worst-case scenario in Chicago, but only with strong mitigation/lockdown implemented in the next week at the latest. If this window is missed, the epidemic will get worse and then strong mitigation/lockdown will be required after all, but it will be too late.

negative: Lack of Antiviral Activity of Darunavir against SARS-CoV-2 Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 = 0.38 μM). Overall, the data do not support the use of DRV for treatment of COVID-19.

negative: Culture counts: The diverse effects of culture and society on mental health amidst COVID-19 outbreak in Australia.

negative: Report from the COVID-19 Virtual Summit, Disaster Experts Speak Out, March 31, 2020 This article captures the webinar narrative on March 31, 2020 of four expert panelists addressing three questions on the current coronavirus disease 2019 (COVID-19) pandemic. Each panelist was selected for their unique personal expertise, ranging from front-line emergency physicians from multiple countries, an international media personality, former director of the US Strategic National Stockpile, and one of the foremost international experts in disaster medicine and public policy. The forum was moderated by one of the most widely recognized disaster medical experts in the world. The four panelists were asked three questions regarding the current pandemic as follows: 1. What do you see as a particular issue of concern during the current pandemic? 2. What do you see as a particular strength during the current pandemic? 3. If you could change one thing about the way that the pandemic response is occurring, what would you change?

negative: Neglected major causes of death much deadlier than COVID-19

negative: The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis Abstract Apoptosis, necroptosis and pyroptosis represent three distinct types of regulated cell death forms, which play significant roles in response to viral and bacterial infections. Whereas apoptosis is characterized by cell shrinkage, nuclear condensation, bleb formation and retained membrane integrity, necroptosis and pyroptosis exhibit osmotic imbalance driven cytoplasmic swelling and early membrane damage. These three cell death forms exert distinct immune stimulatory potential. The caspase driven apoptotic cell demise is considered in many circumstances as anti-inflammatory, whereas the two lytic cell death modalities can efficiently trigger immune response by releasing damage associated molecular patterns to the extracellular space. The relevance of these cell death modalities in infections can be best demonstrated by the presence of viral proteins that directly interfere with cell death pathways. Conversely, some pathogens hijack the cell death signaling routes to initiate a targeted attack against the immune cells of the host, and extracellular bacteria can benefit from the destruction of intact extracellular barriers upon cell death induction. The complexity and the crosstalk between these cell death modalities reflect a continuous evolutionary race between pathogens and host. This chapter discusses the current advances in the research of cell death signaling with regard to viral and bacterial infections and describes the network of the cell death initiating molecular mechanisms that selectively recognize pathogen associated molecular patterns.

negative: Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza IMPORTANCE: Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. OBJECTIVE: To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. DESIGN: A retrospective cohort study. SETTING: Two academic hospitals in New York City. PARTICIPANTS: We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). EXPOSURES: Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. RESULTS: Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). CONCLUSIONS AND RELEVANCE: Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.

negative: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = −0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [−7.50% (95% CI: −10.99%, −3.88%) and −11.41% (95% CI: −19.68%, −2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.

negative: The fiscal value of human lives lost from Novel Coronavirus (2019-nCoV) in China According to the WHO coronavirus disease (COVID-19) situation report 35, as of 24th February 2020, there was a total of 77,262 confirmed COVID-19 cases in China That included 2595 deaths The specific objective of this study was to estimate the fiscal value of human lives lost due to COVID-19 in China as of 24th February 2020 The deaths from COVID-19 had a discounted (at 3%) total fiscal value of Int$ 924,346,795 in China Out of which, 63 2% was borne by people aged 25–49 years, 27 8% by people aged 50–64 years, and 9 0% by people aged 65 years and above The average fiscal value per death was Int$ 356,203 Re-estimation of the economic model alternately with 5% and 10 discount rates led to a reduction in the expected total fiscal value by 21 3% and 50 4%, respectively Furthermore, the re-estimation of the economic model using the world’s highest average life expectancy of 87 1 years (which is that of Japanese females), instead of the national life expectancy of 76 4 years, increased the total fiscal value by Int$ 229,456,430 (24 8%)

negative: Trends in 30-Day Readmission Rates for Medicare and Non-Medicare Patients in the Era of the Affordable Care Act Abstract Background Temporal changes in the readmission rates for patient groups and conditions that were not directly under the purview of the Hospital Readmissions Reduction Program (HRRP) can help assess whether efforts to lower readmissions extended beyond targeted patients and conditions. Methods Using the Nationwide Readmissions Database (2010-2015), we assessed trends in all-cause readmission rates for 1 of the 3 HRRP conditions (acute myocardial infarction, heart failure, pneumonia) or conditions not targeted by the HRRP in age-insurance groups defined by age group (≥65 years or <65 years) and payer (Medicare, Medicaid, or private insurance). Results In the group aged ≥65 years, readmission rates for those covered by Medicare, Medicaid, and private insurance decreased annually for acute myocardial infarction (risk-adjusted odds ratio [OR; 95% confidence interval] among Medicare patients, 0.94 [0.94-0.95], among Medicaid patients, 0.93 [0.90-0.97], and among patients with private-insurance, 0.95 [0.93-0.97]); heart failure (ORs, 0.96 [0.96-0.97], 0.96 [0.94-0.98], and 0.97 [0.96-0.99], for the 3 payers, respectively), and pneumonia (ORs, 0.96 [0.96-0.97), 0.94 [0.92-0.96], and 0.96 [0.95-0.97], respectively). Readmission rates also decreased in the group aged <65 years for acute myocardial infarction (ORs: Medicare 0.97 [0.96-0.98], Medicaid 0.94 [0.92-0.95], and private insurance 0.93 [0.92-0.94]), heart failure (ORs, 0.98 [0.97-0.98]: 0.96 [0.96-0.97], and 0.97 [0.95-0.98], for the 3 payers, respectively), and pneumonia (ORs, 0.98 [0.97-0.99], 0.98 [0.97-0.99], and 0.98 [0.97-1.00], respectively). Further, readmission rates decreased significantly for non-target conditions. Conclusions There appears to be a systematic improvement in readmission rates for patient groups beyond the population of fee-for-service, older, Medicare beneficiaries included in the HRRP.

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: Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19 • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce the use of mechanical ventilation . • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce hospital length of stay and length of stay in ICU. • Initiation of IVIG as adjuvant treatment for COVID-19 pneumonia within 48 hours of admission to the ICU can reduce 28-day mortality of patients with severe COVID-19 pneumonia.

negative: COVID‐19 in context: Why do people die in emergencies? It’s probably not because of collective psychology Notions of psychological frailty have been at the forefront of debates around the public response to the COVID‐19 pandemic. In particular, there is the argument that collective selfishness, thoughtless behaviour, and over‐reaction would make the effects of COVID‐19 much worse. The same kinds of claims have been made in relation to other kinds of emergencies, such as fires, earthquakes, and sinking ships. We argue that in these cases as well as in the case of the COVID‐19 pandemic, other factors are better explanations for fatalities – namely under‐reaction to threat, systemic or structural factors, and mismanagement. Psychologizing disasters serves to distract from the real causes and thus from who might be held responsible. Far from being the problem, collective behaviour in emergencies – including the solidarity and cooperation so commonly witnessed among survivors – is the solution, one that should be harnessed more effectively in policy and practice.

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

negative: Transformed time series analysis of first-wave COVID-19: universal similarities found in the Group of Twenty (G20) Countries As of April 30, 2020, the number of cumulative confirmed coronavirus disease 2019 (COVID-19) cases exceeded 3 million worldwide and 1 million in the US with an estimated fatality rate of more than 7 percent. Because the patterns of the occurrence of new confirmed cases and deaths over time are complex and seemingly country-specific, estimating the long-term pandemic spread is challenging. I developed a simple transformation algorithm to investigate the characteristics of the case and death time series per nation, and described the universal similarities observed in the transformed time series of 19 nations in the Group of Twenty (G20). To investigate the universal similarities among the cumulative profiles of confirmed cases and deaths of 19 individual nations in the G20, a transformation algorithm of the time series data sets was developed with open-source software programs. The algorithm was used to extract and analyze statistical information from daily updated COVID-19 pandemic data sets from the European Centre for Disease Prevention and Control (ECDC). Two new parameters for each nation were suggested as factors for time-shifting and time-scaling to define reduced time, which was used to quantify the degree of universal similarities among nations. After the cumulative confirmed case and death profiles of a nation were transformed by using reduced time, most of the 19 nations, with few exceptions, had transformed profiles that closely converged to those of Italy after the onset of cases and deaths. The initial profiles of the cumulative confirmed cases per nation universally showed 3 - 4 week latency periods, during which the total number of cases remained at approximately ten. The latency period of the cumulative number of deaths was approximately half the latency number of cumulative cases, and subsequent uncontrollable increases in human deaths seemed unavoidable because the coronavirus had already widely spread. Immediate governmental actions, including responsive public-health policy-making and enforcement, are observed to be critical to minimize (and possibly stop) further infections and subsequent deaths. In the pandemic spread of infectious viral diseases, such as COVID-19 studied in this work, different nations show dissimilar and seemingly uncorrelated time series profiles of infected cases and deaths. After these statistical phenomena were viewed as identical events occurring at a distinct rate in each country, the reported algorithm of the data transformation using the reduced time revealed a nation-independent, universal profile (especially initial periods of the pandemic spread) from which a nation-specific, predictive estimation could be made and used to assist in immediate public-health policy-making.

negative: What is the people posting about symptoms related to Coronavirus in Bogota, Colombia? During the last months, there is an increasing alarm about a new mutation of coronavirus, covid-19 coined by World Health Organization(WHO) with an impact in many areas: economy, health, politics and others. This situation was declared a pandemic by WHO, because of the fast expansion over many countries. At the same time, people is using Social Networks to express what they think, feel or experiment, so this people are Social Sensors and helps to analyze what is happening in their city. The objective of this paper is analyze the publications of Colombian people living in Bogota with a radius of 50 km using Text Mining techniques from symptomatology approach. The results support the understanding of the spread in Colombia related to symptoms of covid19.

negative: The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C. The recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-SCHM) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-SBJ) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SPBJ) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3' untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTRBJ) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants.IMPORTANCE The recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.

negative: After 2015: infectious diseases in a new era of health and development Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.

negative: The emotional impact of COVID-19: From medical staff to common people

negative: Initial rapid and proactive response for the COVID-19 outbreak — Taiwan's experience

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: Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia BACKGROUND: A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. METHODS: We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. RESULTS: Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10(−4)-2000 TCID(50)/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. CONCLUSIONS: The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.

negative: Heat-Related Deaths - United States, 2004-2018 Deaths attributable to natural heat exposure, although generally considered preventable (1), represent a continuing public health concern in the United States. During 2004-2018, an average of 702 heat-related deaths occurred in the United States annually. To study patterns in heat-related deaths by age group, sex, race/ethnicity, and level of urbanization, and to explore comorbid conditions associated with deaths resulting from heat exposure, CDC analyzed nationally comprehensive mortality data from the National Vital Statistics System (NVSS).* The rate of heat-related mortality tended to be higher among males, persons aged ≥65 years, non-Hispanic American Indian/Alaska Natives, and persons living in noncore nonmetropolitan and large central metropolitan counties. Natural heat exposure was a contributing cause of deaths attributed to certain chronic medical conditions and other external causes. Preparedness and response initiatives directed toward extreme heat events, currently underway at local, state, and national levels, can contribute to reducing morbidity and mortality associated with natural heat exposure. Successful public health interventions to mitigate heat-related deaths include conducting outreach to vulnerable communities to increase awareness of heat-related symptoms and provide guidance for staying cool and hydrated, particularly for susceptible groups at risk such as young athletes and persons who are older or socially isolated (2). Improved coordination across various health care sectors could inform local activities to protect health during periods of high heat. For instance, jurisdictions can monitor weather conditions and syndromic surveillance data to guide timing of risk communication and other measures (e.g., developing and implementing heat response plans, facilitating communication and education activities) to prevent heat-related mortality in the United States. CDC also recommends that federal, state, local, and tribal jurisdictions open cooling centers or provide access to public locations with air conditioning for persons in need of a safe, cool, environment during hot weather conditions. In light of the coronavirus disease 2019 (COVID-19) pandemic, CDC updated its guidance on the use of cooling centers to provide best practices (e.g., potential changes to staffing procedures, separate areas for persons with symptoms of COVID-19, and physical distancing) to reduce the risk for introducing and transmitting SARS COV-2, the virus that causes COVID-19, into cooling centers.§.

negative: COVID-19: Projecting the impact in Rohingya refugee camps and beyond Background: COVID-19 could have even more dire consequences among refugees living in camps than in general populations. Bangladesh has confirmed COVID-19 cases and hosts almost 1 million Rohingya refugees from Myanmar with 600,000 concentrated in Kutupalong-Balukhali Expansion Site. Projections of the potential COVID-19 infection burden, epidemic speed, and healthcare needs in such settings are critical to inform preparedness planning. Methods: To explore the potential impact of the introduction of SARS-CoV-2 in Kutupalong-Balukhali Expansion Site, we used a stochastic disease transmission model with parameters derived from emerging literature. We considered three scenarios with different assumptions about the transmission potential of SARS-CoV-2. We estimated the number and daily rate of infections, hospitalizations, deaths, and healthcare needs expected under each scenario. Findings: A large-scale outbreak is highly likely after a single introduction of the virus into the camp across scenarios with 65-95% of simulations leading to at least 1,000 infections. Estimated infections range from 119-504 between low and high transmission scenarios in the first 30 days; and between 424,798 and 543,647 in 12 months. Hospitalization needs exceeded the existing hospitalization capacity of 340 beds after 58-139 days between the low and high transmission scenarios. Estimated deaths range from 1,647-2,109 between low and high transmission scenarios. Interpretation: A COVID-19 epidemic in a refugee settlement may have profound consequences, requiring unrealistically large increases in healthcare capacity and infrastructure. Detailed and realistic planning for the worst in Kutupalong-Balukhali and all refugee camps worldwide must begin now. Plans should consider novel and radical strategies to reduce infectious contacts and fill health worker gaps while recognizing that refugees may not have access to national health systems. As global resources to fight this pandemic become scarce, displaced persons must not be forgotten.

negative: Success of Big Infectious Disease Reimbursement Policy in China Big infectious diseases do harm to the whole society, and it is highly crucial to control them on time. The major purpose of this article is to theoretically demonstrate that the Chinese government’s intervention in large-scale infectious diseases is successful and efficient. Two potential strategies were considered: strategy 1 was infectious disease without government intervention, and strategy 2 was infectious disease with government intervention. By evolution model, this article illustrates the efficiency of big infectious disease reimbursement policy in China. Without government reimbursement, this article finds that high expenditures accelerate the disease infection. The number of infected persons decreases under big infectious disease reimbursement policy in China. The higher the treatment costs, the more important the government intervention. Big infectious disease reimbursement policy in China can serve as an efficient example to cope with big infectious diseases.

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: La comunicación científica y el acceso abierto en la contención de enfermedades: El caso del Coronavirus novel 2019 (2019-nCoV)

negative: COVID-19 and Italy: what next? The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. A global response to prepare health systems worldwide is imperative. Although containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, and Italy has been particularly affected. There is now grave concern regarding the Italian national health system's capacity to effectively respond to the needs of patients who are infected and require intensive care for SARS-CoV-2 pneumonia. The percentage of patients in intensive care reported daily in Italy between March 1 and March 11, 2020, has consistently been between 9% and 11% of patients who are actively infected. The number of patients infected since Feb 21 in Italy closely follows an exponential trend. If this trend continues for 1 more week, there will be 30 000 infected patients. Intensive care units will then be at maximum capacity; up to 4000 hospital beds will be needed by mid-April, 2020. Our analysis might help political leaders and health authorities to allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. If the Italian outbreak follows a similar trend as in Hubei province, China, the number of newly infected patients could start to decrease within 3–4 days, departing from the exponential trend. However, this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in China.

negative: Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission

negative: The impact of Covid-19 pandemic on corporate social responsibility and marketing philosophy In this article, we offer some initial examination on how Covid-19 pandemic can influence the developments of CSR and marketing. We argue that Covid-19 pandemic offers a great opportunity for businesses to shift towards more genuine and authentic CSR and contribute to address urgent global social and environmental challenges. We also discuss some potential directions of how consumer ethical decision making will be shifted to due to the pandemic. In our discussion of marketing, we outline how we believe marketing is being affected by this pandemic and how we think this will change, not only the context of marketing, but how organizations approach their strategic marketing efforts. We end the paper with a identifying a number of potentially fruitful research themes and directions.

negative: Clinical and virological data of the first cases of COVID-19 in Europe: a case series BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log(10) copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases).

negative: Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States Coronavirus disease 2019 (Covid-19) has devastated global populations and has had a large impact in the United States with the number of infections and deaths growing exponentially. Using a smooth generalized additive model with quasipoisson counts for total infections and deaths, we developed a county-level predictive model that included population demographics, social characteristics, social distancing, and testing data. This model strongly predicted the actual US distribution of Covid-19, accounting for 94.8% of spatial-temporal variation in total infections and 99.3% in Covid-19 related fatalities from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans had a higher number of confirmed infections adjusted for county population. Social distancing measured by the change in the rate of human encounter per km2 relative to pre-covid-19 national average was associated with slower rate of Covid-19 infections, whereas higher testing was associated with higher number of infections. The number of people infected was increasing, however, the rate of increase in new infections was starting to show signs of plateauing starting from the second week of April. Our model projects 2.11 million people to test positive for Covid-19 and 122,951 fatalities by June 1, 2020. Importantly, our model suggests strong social differences in the infections and deaths across US communities, and inequities in areas with larger African American minorities and higher poverty index expected to show higher rates of Covid-19 infections and deaths. Preventive steps including social distancing and community closures have been a cornerstone in stopping the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in the disease transmission is essential to understand current disease distribution, predict future distribution, and plan additional preventive steps.

negative: Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.

negative: From Diversity to Coordination: A European Approach to COVID-19 The COVID-19 pandemic is changing the face of Europe. Member States’ divergent responses to this crisis reveal a lack of unity in the face of a humanitarian catastrophe. At best, this undermines the effectiveness of health protection within the European Union (EU). At worst, it risks breaking up the Union altogether. Divergent national responses to COVID-19 reflect different national preferences and political legitimacy, and thus cannot be completely avoided. In this article, we argue that these responses should be better coordinated. Without coordination, the price for diversity is high. Firstly, there are damaging spill-overs between Member States, which undermine key pillars of European integration such as the free movement of persons and of goods. Secondly, national policy-making is easily captured by local interest groups. Our proposal is that the EU indicates – not mandates – a European exit strategy from asymmetric containment policies of COVID-19. In particular, the EU should help Member States procure and validate tests for infection and immunity. The EU should also indicate ways in which testing could be used to create safe spaces to work, thereby restoring the free movement of persons and of goods. We see a great advantage in such EU guidance: it could improve mutual learning between Member States, which have faced different timings of the epidemic and learned different lessons. Although the local political economy has so far delayed learning and undermined cooperation, the EU can mitigate both effects and indicate the way for Europe to resurrect united from the ashes of COVID-19.

negative: Covid-19 pandemic and the skin - What should dermatologists know? Abstract The World has changed dramatically since the COVID-19 pandemic began. Together with our social, occupational, and personal life, the new corona virus poses novel challenges for all physicians, including dermatologists. Despite the virus not being dermatotropic, several skin conditions have emerged, mainly as a result of prolonged contact to personal protective equipment and excessive personal hygiene. Pressure injury, contact dermatitis, itch, pressure urticaria, and exacerbation of pre-existing skin diseases, including seborrheic dermatitis and acne, have been described. We have focused on the dermatologic aspects of COVID-19 infection, so that dermatologist may be aware of the skin complications and the preventive measures to be taken in the COVID-19 pandemic.

negative: Coronaviruserkrankung 2019 (COVID-19) und Schwangerschaft: Übersicht und Bericht des ersten deutschen Falls mit COVID-19 bei Gestationsdiabetes Since the beginning of the coronavirus pandemic with SARS-CoV‑2 (severe acute respiratory syndrome coronavirus 2) in January 2020, more than 100 cases of pregnant Chinese women have been published, including individuals with gestational diabetes (GDM). The descriptive overview reports on the clinical presentation of COVID-19 as well as on obstetric and neonatal outcome data. The main symptoms of the overall milder course of infection are fever, cough and dyspnea. So far, there is no evidence of intrauterine transmission of the virus and no evidence of breast milk transfer. Postnatal infections of infants of infected mothers are documented, but the course is usually mild. The available data are informative for preparing health professionals for the expected infections in pregnant women with the comorbidity diabetes mellitus.

negative: Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd Abstract In 2012 in Jordan, infection by a novel coronavirus (CoV) caused the first known cases of Middle East respiratory syndrome (MERS). MERS-CoV sequences have since been found in a bat and the virus appears to be enzootic among dromedary camels across the Arabian Peninsula and in parts of Africa. The majority of human cases have occurred in the Kingdom of Saudi Arabia (KSA). In humans, the etiologic agent, MERS-CoV, has been detected in severe, mild and influenza-like illness and in those without any obvious signs or symptoms of disease. MERS is often a lower respiratory tract disease associated with fever, cough, breathing difficulties, pneumonia that can progress to acute respiratory distress syndrome, multiorgan failure and death among more than a third of those infected. Severe disease is usually found in older males and comorbidities are frequently present in cases of MERS. Compared to SARS, MERS progresses more rapidly to respiratory failure and acute kidney injury, is more often observed as severe disease in patients with underlying illnesses and is more often fatal. MERS-CoV has a broader tropism than SARS-CoV, rapidly triggers cellular damage, employs a different receptor and induces a delayed proinflammatory response in cells. Most human cases have been linked to lapses in infection prevention and control in healthcare settings, with a fifth of virus detections reported among healthcare workers. This review sets out what is currently known about MERS and the MERS-CoV, summarises the new phenomenon of crowd-sourced epidemiology and lists some of the many questions that remain unanswered, nearly three years after the first reported case.

negative: Going viral – Covid-19 impact assessment: A perspective beyond clinical practice In the realm of infectious diseases, a global outbreak is a worst-case scenario In the past, outbreaks such as plague, Spanish flu, severe acute respiratory syndrome, and H1N1 (swine flu) have caused great human suffering The novel coronavirus, christened as Covid-19, is a zoonotic disease which originated from the Wuhan province in China and spread like wildfire killing people and devastating the global economy Mammoth efforts are still on to control this viral strain from further spread Cities have been blocked, air travel banned, ships have been quarantined, and panic-stricken people have been evacuated from China As Covid-19 continues to ravage countries across the globe, this article is an effort to provide an overview of the impact of Covid-19 and tickle wits of intellectuals to think how easily a nanometer organism can virtually bring down superpowers of the world

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

negative: Chatbots in the fight against the COVID-19 pandemic We are all together in a fight against the COVID-19 pandemic. Chatbots, if effectively designed and deployed, could help us by sharing up-to-date information quickly, encouraging desired health impacting behaviors, and lessening the psychological damage caused by fear and isolation. Despite this potential, the risk of amplifying misinformation and the lack of prior effectiveness research is cause for concern. Immediate collaborations between healthcare workers, companies, academics and governments are merited and may aid future pandemic preparedness efforts.

negative: Excess registered deaths in England and Wales during the COVID-19 pandemic, March 2020 to May 2020 Official counts of COVID-19 deaths have been criticized for potentially including people who did not die of COVID-19 but merely died with COVID-19. I address that critique by fitting a generalized additive model to weekly counts of all deaths registered in England and Wales during the 2010s. The model produces baseline rates of death registrations expected without the COVID-19 pandemic, and comparing those baselines to recent counts of registered deaths exposes the emergence of excess deaths late in March 2020. By April's end, England and Wales registered 45,300 $\pm$ 3200 excess deaths of adults aged 45+. Through 22 May, the last day of available all-deaths data, 56,600 $\pm$ 4400 were registered (about 53% of which were of men). Both the ONS's corresponding count of 43,205 death certificates which mention COVID-19, and the Department of Health and Social Care's count of 33,671 deaths, are appreciably less, implying that their counting methods have underestimated, not overestimated, the pandemic's true death toll. If underreporting rates have held steady during May, about 59,000 direct and indirect COVID-19 deaths might have been registered through the end of May but not yet publicly reported in full.

negative: Ecosystem approaches to the risk for schizophrenia

negative: Viruses In the past, viruses were considered nonliving infectious particles, little more than genetic material wrapped in a protein capsid. Today, virologists are beginning to think of viruses as living organisms that can be classified phylogenetically into defined species, much like any other living organism. The primary reasons for this shift in attitude can be partially attributed to the discovery of giant viruses, having large genomes and complex regulatory systems. Aside from that, it has become obvious that viruses lead complex lives; they evolve, speciate, and participate in the evolution of all classes of living organisms. In this chapter, we will discuss the early attempts to classify viruses, and review the biologic properties of the classes of virus that contain human pathogens.

negative: Außerklinische Beatmung: Lungenerkrankungen In den letzten Jahren ist eine deutliche und kontinuierliche Zunahme von meist schwerkranken Patienten zu konstatieren, die außerhalb einer Klinik beatmet werden. Diese Patienten stellen eine wachsende Herausforderung für alle an der Versorgung Beteiligten dar. In der Regel erfolgt die ärztliche Weiterbetreuung und die Verordnung der benötigten Hilfsmittel durch Hausärzte. In diesem Beitrag lesen Sie, was ein Hausarzt aus dem Bereich der Beatmungsmedizin wissen sollte.

negative: [An update on the epidemiological characteristics of novel coronavirus pneumonia（COVID-19）]. Through literature review and group discussion, Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine Association formulated an update on the epidemiological characteristics of novel coronavirus pneumonia (NCP). The initial source of the 2019 novel coronavirus (2019-nCoV) was the Huanan seafood market in Wuhan, Hubei province, China, with pangolins as a potential animal host. Currently the main source of infection is NCP patients, and asymptomatic carriers may also be infectious. The virus is believed transmitted mostly via droplets or contact. People are all generally susceptible to the virus. The average incubation period was 5.2 days, and the basic reproductive number R(0) was 2.2 at the onset of the outbreak. Most NCP patients were clinically mild cases. The case fatality rate was 2.38%, and elderly men with underlying diseases were at a higher risk of death. Strategies for prevention and control of NCP include improving epidemic surveillance, quarantining the source of infection, speeding up the diagnosis of suspected cases, optimizing the management of close contacts, tightening prevention and control of cluster outbreaks and hospital infection, preventing possible rebound of the epidemic after people return to work from the Chinese Spring Festival holiday, and strengthening community prevention and control.

negative: The COVID-19 pandemic from an ophthalmologist’s perspective Abstract The current COVID-19 pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how SARS-Cov2 affects the eye and discuss implications for ophthalmologists.

negative: A “One-Health” approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy Abstract The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. IZSAM, is currently testing more than 600 samples per day and WGS from positive samples. Sequence analysis of these samples suggested that outbreaks in Abruzzo region may be related to outbreaks of northern Italy and northern Europe, these latter as for the presence of mutations in the N protein. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.

negative: The dramatic impact of coronavirus outbreak on air quality: Has it saved as much as it has killed so far? The outbreak of coronavirus disease (COVID-19) was first reported from Wuhan, China, on December 31st, 2019. As the number of coronavirus infections has exceeded 100,000 with toll deaths of about 5000 worldwide as of early March, 2020, scientists and researchers are racing to investigate the nature of this virus and evaluate the short and long term effects of this disease. Despite its negative impacts that obliged the World Health Organization to declare COVID-19 epidemic as a Public Health Emergency of International Concern, the rate of mortality of this infection has not exceeded 3.4% globally. On the other hand, the mortality rate caused by ambient air pollution has contributed to 7.6% of all deaths in 2016 worldwide. The outbreak of COVID-19 has forced China to lockdown its industrial activities and hence dropped its NO2 and carbon emissions by 30 and 25%, respectively. This work reports on the first case study that compares the air quality status before and after the crisis. It sheds light on the facts related to the demographics of deaths by gender, age and health status before infection. The historical data on air quality, estimates of annual deaths and its economic burden have been presented and analyzed. The actual daily deaths due to COVID-19 have been obtained from the official records of the daily Situation Reports published by World Health Organization as of March 11th. The rate of mortality due to COVID-19 was impacted by two factors: age and health status. Results show that 75% of deaths were related to cases that had underlying present diseases with the majority aged of 80+ years. The reported figures were compared with the average daily mortality due to poor air quality which reached up to 3287 deaths due to high levels of NO2, O3 and PM. The air quality status before the crisis was compared with the current situation showing that COVID-19 forced-industrial and anthropogenic activities lockdown may have saved more lives by preventing ambient air pollution than by preventing infection.

negative: Cognitive therapy for post-traumatic stress disorder following critical illness and intensive care unit admission Around a quarter of patients treated in intensive care units (ICUs) will develop symptoms of post-traumatic stress disorder (PTSD). Given the dramatic increase in ICU admissions during the COVID-19 pandemic, clinicians are likely to see a rise in post-ICU PTSD cases in the coming months. Post-ICU PTSD can present various challenges to clinicians, and no clinical guidelines have been published for delivering trauma-focused cognitive behavioural therapy with this population. In this article, we describe how to use cognitive therapy for PTSD (CT-PTSD), a first line treatment for PTSD recommended by the National Institute for Health and Care Excellence. Using clinical case examples, we outline the key techniques involved in CT-PTSD, and describe their application to treating patients with PTSD following ICU. KEY LEARNING AIMS: 1. To recognise PTSD following admissions to intensive care units (ICUs). 2. To understand how the ICU experience can lead to PTSD development. 3. To understand how Ehlers and Clark’s (2000) cognitive model of PTSD can be applied to post-ICU PTSD. 4. To be able to apply cognitive therapy for PTSD to patients with post-ICU PTSD.

negative: LA PSIQUIATRÍA EN LAS SECUELAS DE COVID-19 Resumen La pandemia por Covid-19 ha obligado a modificar sustancialmente la forma de trabajar de los profesionales de la salud mental y puede tener un impacto diferido sobre los pacientes. La Psiquiatría post-Covid-19 pondrá en valor la especialidad como parte de la medicina, los aspectos psicológicos de la práctica médica, la psiquiatría de enlace e interconsulta hospitalaria, la atención domiciliaria, y la atención ambulatoria virtual o telemática. Las consecuencias del confinamiento poblacional, el duelo por las muertes solitarias, y el impacto de la crisis sanitaria sobre los profesionales de la salud mental, desde los dispositivos hospitalarios hasta los comunitarios, de rehabilitación, y la atención primaria, centrarán nuestros esfuerzos durante el desescalado y el medio plazo. Es previsible un aumento de la demanda de atención psiquiátrica a medio y largo plazo y un impacto en la docencia e investigación en salud mental. Abstract The COVID-19 pandemic has forced mental health professionals to substantially change the way they work and may have a delayed impact on patients. The aftermath of COVID-19 will shine a light on certain aspects of psychiatry addressed in this article: psychiatry as a medical specialty, the psychological aspects of medical practice, liaison and consultative psychiatry, home hospitalization, and virtual or telemedicine outpatient care. The consequences of population lockdown, complicated grief over solitary deaths, and the impact of the health crisis on mental health professionals – from hospitals to community services, rehabilitation facilities, and primary care – will be the focus of our efforts during the period of lockdown easing and in the medium term. There will be a foreseeable increase in demand for psychiatric care in the medium and long term along with an impact on mental health education and research.

negative: Novel Antiretroviral Structures from Marine Organisms In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.

negative: Is a COVID19 Quarantine Justified in Chile or USA Right Now? During the current COVID-19 pandemic it is imperative to give early warnings to reduce mortality. However, non-specialist such as authorities and the general population face several problems to understand the real thread of this pandemic, and under/overestimation of its risk are a commonplace in the press and social media. Here we define an index, which we call the COVID-19 Burden Index, that relates the capacities of the healthcare system of a given country to treat severe and critical cases. Its value is 0 if there is no extra strain in the healthcare system, and it reaches 1.0 when the collapse is imminent. As of 23 March 2020, we show that Chile, the USA, UK, among other countries, must reduce the rate of infections right now, otherwise, in less than 7 days they could be in a catastrophic situation such as Italy, Spain and Iran.

negative: COVID-19 and homelessness in England: a modelling study of theCOVID-19 pandemic among people experiencing homelessness, and theimpact of a residential intervention to isolate vulnerable people andcare for people with symptoms Background: There is an ongoing pandemic of the viral respiratory disease COVID-19. People experiencing homelessness are vulnerable to infection and severe disease. Health and housing authorities in England have developed a residential intervention that aims to isolate those vulnerable to severe disease (COVID-PROTECT) and care for people with symptoms (COVID CARE). Methods: We used a discrete-time Markov chain model to forecast COVID-19 infections among people experiencing homelessness, given strong containment measures in the general population and some transmission among 35,817 people living in 1,065 hostels, and 11,748 people sleeping rough (the 'do nothing' scenario). We then estimated demand for beds if those eligible are offered COVID-PROTECT and COVID-CARE. We estimated the reduction in the number of COVID-19 cases, deaths, and hospital admissions that could be achieved by these interventions. We also conducted sensitivity and scenario analyses to identify programme success factors. Results: In a 'do nothing' scenario, we estimate that 34% of the homeless population could get COVID-19 between March and August 2020, with 364 deaths, 4,074 hospital admissions and 572 critical care admissions. In our 'base intervention' scenario, demand for COVID-PROTECT peaks at 9,934 beds, and demand for COVID-CARE peaks at 1,366 beds. The intervention could reduce transmission by removing symptomatic individuals from the community, and preventing vulnerable individuals from being infected. This could lead to a reduction of 164 deaths, 2,624 hospital admissions, and 248 critical care admissions over this period. Sensitivity analyses showed that the number of deaths is sensitive to transmission of COVID-19 in COVID-PROTECT. If COVID-PROTECT capacity is limited, scenario analyses show the benefit of prioritising people who are vulnerable to severe disease. Conclusion: Supportive accommodation can mitigate the impact of the COVID-19 pandemic on the homeless population of England, and reduce the burden on acute hospitals.

negative: Neural network based country wise risk prediction of COVID-19 The recent worldwide outbreak of the novel corona-virus (COVID-19) opened up new challenges to the research community. Artificial intelligence (AI) driven methods can be useful to predict the parameters, risks, and effects of such an epidemic. Such predictions can be helpful to control and prevent the spread of such diseases. The main challenges of applying AI is the small volume of data and the uncertain nature. Here, we propose a shallow Long short-term memory (LSTM) based neural network to predict the risk category of a country. We have used a Bayesian optimization framework to optimized and automatically design country-specific networks. We have combined the trend data and weather data together for the prediction. The results show that the proposed pipeline outperforms against state-of-the-art methods for 170 countries data and can be a useful tool for such risk categorization. The tool can be used to predict long-duration outbreak of such an epidemic such that we can take preventive steps earlier.

negative: H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. These results together show that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection. In addition, primary macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro and in infected mouse lung tissue.

negative: On the assessment of more reliable COVID-19 infected number: the italian case. COVID-19 (SARS-CoV-2) is the most recent pandemic disease the world is currently managing. It started in China at the end of 2019, and it is diffusing throughout Italy, one of the most affected countries, and it is currently spreading through European countries and USA. Patients affected by COVID-19 are identified employing medical swabs applied mainly to (i) citizens with COVID-19 symptoms such as flu or high temperature, or (ii) citizens that had contacts with COVID-19 patients. A percentage of COVID-19 affected patients needs hospitalisation, whereas a portion needs to be treated in Intensive Care Units (ICUs). Nevertheless, it is a matter of current intuition that COVID-19 infected citizens are more than those detected, and sometime the infection is detected too late. Thus there are many efforts in both tracking people activities as well as diffusing low cost reliable COVID-19 tests for early detection. Starting from mortality rates of diseases caused by viruses in the same family (e.g. MERS, SARS, H1N1), we study the relations between the number of COVID-19 infections and the number of deaths, through Italian regions. We thus assess several infections being higher than the ones currently measured. We thus focus on the characterisation of the pandemic diffusion by estimating the infected number of patients versus the number of death. We use such an estimated number of infections, to foresee the effects of restriction actions adopted by governments to constrain virus diffusion. We finally think that our model can support the healthcare system to react when COVID-19 is increasing.

negative: The Mortality and Psychological Burden Caused by Response to COVID-19 Outbreak: a Hypothesis and a Crude Estimation The world is experiencing a severe COVID-19 outbreak. To control this outbreak, many governments in the world have imposed lockdown or quarantine measures. We hypothesize that these measures may cause additional mortality and morbidity in the (near) future due to delay in diagnosing diseases and other indirect effect on health (such as economic crisis). To support this hypothesis and to estimate the additional mortality that may linked to the COVID-19 controlling policy, we performed a step-by-step pragmatical approach. First, we chose a country (The Netherlands), and looked at the most common causes of mortality in that country. Then, we performed a literature study on the additional mortality when these causes were diagnosed late, and selected a paper with the most severe scenario. We also performed a literature study on the effect of economic crisis on additional mortality. The mortality data were then extrapolated to the demography of The Netherlands, and the results were compared with the present data on deaths directly due to COVID-19. Roughly we forecast 388 additional deaths a week in The Netherlands for the period of 5 years due to the direct and indirect effects of the lockdown measures. To support the hypothesis on the effect of COVID-19 curbing measures on mental health, we performed literature search on quarantine policy during precious SARS-CoV-2 outbreak. The most important implications of this hypothesis is that the additional mortality and increased mental health problem should be considered in evaluating the necessity of lock down and quarantine policy.

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: Modelling SARS-COV2 Spread in London: Approaches to Lift the Lockdown Abstract Objective To use mathematical models to predict the epidemiological impact of lifting the lockdown in London, UK, and alternative strategies to help inform policy in the UK. Methods A mathematical model for the transmission of SARS-CoV2 in London. The model was parametrised using data on notified cases, deaths, contacts, and mobility to analyse the epidemic in the UK capital. We investigated the impact of multiple non pharmaceutical interventions (NPIs) and combinations of these measures on future incidence of COVID-19. Results Immediate action at the early stages of an epidemic in the affected districts would have tackled spread. While an extended lockdown is highly effective, other measures such as shielding older populations, universal testing and facemasks can all potentially contribute to a reduction of infections and deaths. However, based on current evidence it seems unlikely they will be as effective as continued lockdown. In order to achieve elimination and lift lockdown within 5 months, the best strategy seems to be a combination of weekly universal testing, contact tracing and use of facemasks, with concurrent lockdown. This approach could potentially reduce deaths by 48% compared with continued lockdown alone. Conclusions A combination of NPIs such as universal testing, contact tracing and mask use while under lockdown would be associated with least deaths and infections. This approach would require high uptake and sustained local effort but it is potentially feasible as may lead to elimination in a relatively short time scale.

negative: Optimal Control Design of Impulsive SQEIAR Epidemic Models with Application to COVID-19 quarantined individuals (Q), called SQEIAR model. The dynamic of SQEIAR model is defined by six ordinary differential equations that describe the numbers of Susceptible, Quarantined, Exposed, Infected, Asymptomatic, and Recovered individuals. The goal of this paper is to reduce the size of susceptible, infected, exposed and asymptomatic groups to consequently eradicate the infection by using two actions: the quarantine and the treatment of infected people. To reach this purpose, optimal control theory is presented to control the epidemic model over free terminal optimal time control with an optimal cost. Pontryagin's maximum principle is used to characterize the optimal controls and the optimal final time. Also, an impulsive epidemic model of SQEIAR is considered to deal with the potential suddenly increased in population caused by immigration or travel. Since this model is suitable to describe the COVID-19 pandemic, especial attention is devoted to this case. Thus, numerical simulations are given to prove the accuracy of the theoretical claims and applied to the particular data of this infection. Moreover, numerical computations of the COVID-19 are compared with diseases like Ebola and Influenza. In addition, the controller is evaluated with system parameters identified by using actual data of China. Finally, the controller tuned with the estimated parameters of the Chinese data is applied to the actual data of Spain to compare the quarantine and treatment policies in both countries.

negative: Estimating Risk for Death from Coronavirus Disease, China, January–February 2020 Since December 2019, when the first case of coronavirus disease (COVID-19) was identified in the city of Wuhan in the Hubei Province of China, the epidemic has generated tens of thousands of cases throughout China. As of February 28, 2020, the cumulative number of reported deaths in China was 2,858. We estimated the time-delay adjusted risk for death from COVID-19 in Wuhan, as well as for China excluding Wuhan, to assess the severity of the epidemic in the country. Our estimates of the risk for death in Wuhan reached values as high as 12% in the epicenter of the epidemic and ≈1% in other, more mildly affected areas. The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control.

negative: Covid-19 testing strategies and lockdowns: the European closed curves, analysed by ``skew-normal'' distributions, the forecasts for the UK, Sweden, and the USA, and the ongoing outbreak in Brazil. As the number of Covid-19 infections worldwide overtakes 6 millions of Total Confirmed Cases (TCC), the data reveal almost closed outbreaks in many European countries. Using the European data as a basis for our analysis, we study the spreading rate of Covid-19 and model the Daily Confirmed Cases and Deaths per Million (DCCpM and DDpM) curves by using ``skew-normal'' probability density functions. The use of these asymmetrical distributions allows to get a more realistic prediction of the end of the disease in each country and to evaluate the effectiveness of the local authorities strategies in facing the European outbreak. The initial stage of the Brazilian disease is compared with the early phase of the European one. This is done by using the weekly spreading rate of Covid-19. For Sweden, UK, and USA, we shall give a forecast for the end of pandemic and for Brazil the prediction of the peak of DDpM. We also discuss additional factors that could play an important role in the fight against Covid-19, such as the fast response of the local authorities, the testing strategies, the number of beds in the intensive care units, and, last but not least, the measures of isolation adopted. The Brazilian mitigation measures can be placed between the strict lockdown of many European countries and the Swedish approach, but clearly much comparable to the European ones (in particular to the Netherlands). Methods. For Brazil, the weekly spreading rates of Covid-19, as more people are getting infected, was used to compare the outbreak in these countries with the ones of the European countries when they were at the same stage of infection. In the early stage of the disease, normal distributions have been used to obtain what we call a dynamic prediction of the peaks. After reaching the peak of daily infections and/or deaths, skew-normal distributions are required to correctly fit the asymmetrical DCCpM and DDpM curves and get a realistic forecast of the pandemic end. Findings. The European data analysis shows that the spreading rate of Covid-19 increased similarly for all countries in its initial stage, but it changed as the number of TCCpM in each country grew. This was caused by the different timely action of the authorities in adopting isolation measures and/or massive testing strategies. The early stage of the outbreak in the USA and Brazil shows for their $boldsymbol{alpha}$ factor (DCCpM) a behaviour similar to Italy and Sweden, respectively. For the $boldsymbol{beta}$ factor (DDpM), the American spreading is similar to the one of Switzerland, whereas the Brazilian factor is greater than the ones of Portugal, Germany, and Austria (which showed, in terms of TDpM, the best results in Europe) but, at the moment, it is lower than the other European countries. Interpretation. The fitting skew parameters used to model the DCCpM and DDpM curves allow a more realistic prediction of the end of the pandemic and give us the possibility to compare the mitigation measures adopted by the local authorities by analysing their respective skew normal parameters (mean, mode, standard deviation, and skewness). In Europe, Sweden and the UK show the greatest asymmetries, a kind of marathon instead of the sprint of other European countries (as observed by Swedish authorities). This also happens for the USA. The Brazilian weekly spreading rate for deaths is lower than most of the European countries at the same stage of the outbreak.

negative: Finanzieller Schutzschild für Praxen mit Corona-Minus: Entlastungsgesetz Ein neues Bundesgesetz soll die Honorarverluste aufgrund der Coronavirus-Pandemie abfedern. Die Kassen werden verpflichtet, den KVen die volle Gesamtvergütung zu überweisen. Fraglich ist, ob das Geld die richtigen Praxen erreichen wird.

negative: Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.

negative: The race to unravel the United States’ biggest coronavirus outbreak Rohit Shankar left the virology laboratory at 2 a m on Wednesday, and was back at the lab bench by 7 a m the same day “It’s okay,” he says, “I had a doughnut and a coffee ” Shankar, a medical scientist, and his colleagues at the University of Washington in Seattle are poised to exponentially drive up the number of confirmed cases of the coronavirus disease COVID-19 around the city, in western Washington state That’s because this week, they began analysing a mountain of nose and throat swabs collected from hospitals in the region Already, the researchers are seeing clear signs that the virus has infected vastly more people than have been formally detected Scientists fear coronavirus spread in countries least able to contain it Washington state has become the United States’ ground zero for COVID-19, which has now spread to more than 90 countries worldwide in what seems to be a new and dangerous phase of the outbreak Washington has declared a state emergency, and ten people there have died from the disease But the number of confirmed cases in Washington — 70 — is still an underestimate resulting from a lack of testing, researchers agree A genomic analysis posted online on 29 February suggested that hundreds of people in western Washington might already be infected Academic scientists have mostly been prevented from measuring the extent of the US outbreak because of federal rules restricting the number of labs qualified to run diagnostic tests But that is changing now, and helps account for why the state's caseload jumped from 10 to 70 this week Dozens of virologists and genomicists have now kicked into high gear in Seattle, dropping or adapting projects to devote resources to the outbreak Researchers are working around the clock to find out how many people have the disease in the area Others are analysing genomes to reveal how the virus is transmitted or developing new therapies The scientists are racing to help Washington avoid the fate of Hubei province in China, where more than 2,900 people have died of COVID-19 so far The coronavirus emerged in the province’s city Wuhan in December, and the initial response from officials was slow “We are past the point of containment,” says Helen Chu, an infectious-disease specialist at the University of Washington School of Medicine (UW Medicine) in Seattle “So now we need to keep the people who are vulnerable from getting sick ”

negative: Use of Rapid Online Surveys to Assess People's Perceptions During Infectious Disease Outbreaks: A Cross-sectional Survey on COVID-19 BACKGROUND: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate of phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. OBJECTIVE: This study aimed to apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (COVID-19) among the general public in the United States and the United Kingdom. METHODS: An online questionnaire was administered to 3000 adults residing in the United States and 3000 adults residing in the United Kingdom who had registered with Prolific Academic to participate in online research. Prolific Academic established strata by age (18-27, 28-37, 38-47, 48-57, or ≥58 years), sex (male or female), and ethnicity (white, black or African American, Asian or Asian Indian, mixed, or “other”), as well as all permutations of these strata. The number of participants who could enroll in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrollment into the survey within each stratum was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2, 2020. RESULTS: A total of 2986 and 2988 adults residing in the United States and the United Kingdom, respectively, completed the questionnaire. Of those, 64.4% (1924/2986) of US participants and 51.5% (1540/2988) of UK participants had a tertiary education degree, 67.5% (2015/2986) of US participants had a total household income between US $20,000 and US $99,999, and 74.4% (2223/2988) of UK participants had a total household income between £15,000 and £74,999. US and UK participants’ median estimate for the probability of a fatal disease course among those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 5.0% (IQR 2.0%-15.0%) and 3.0% (IQR 2.0%-10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of COVID-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI 36.1%-39.6%) of US participants and 29.7% (95% CI 28.1%-31.4%) of UK participants thought that wearing a common surgical mask was “highly effective” in protecting them from acquiring COVID-19, and 25.6% (95% CI 24.1%-27.2%) of US participants and 29.6% (95% CI 28.0%-31.3%) of UK participants thought it was prudent to refrain from eating at Chinese restaurants. Around half (53.8%, 95% CI 52.1%-55.6%) of US participants and 39.1% (95% CI 37.4%-40.9%) of UK participants thought that children were at an especially high risk of death when infected with SARS-CoV-2. CONCLUSIONS: The distribution of participants by total household income and education followed approximately that of the US and UK general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public’s knowledge and misperceptions during rapidly moving infectious disease outbreaks.

negative: High Risk of COVID-19 Infection for Head and Neck Surgeons

negative: Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection BACKGROUND: Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients. METHODS: We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses. RESULTS: The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality. CONCLUSION: Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.

negative: Death and contagious infectious diseases: Impact of the COVID-19 virus on stock market returns Abstract This study investigates whether contagious infectious diseases affect stock market outcomes. As a natural experiment, we use panel data regression analysis to measure the effect of the COVID-19 virus, which is a contagious infectious disease, on the Chinese stock market. The findings indicate that both the daily growth in total confirmed cases and in total cases of death caused by COVID-19 have significant negative effects on stock returns across all companies.

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: Behavioral Welfare Economics A growing body of normative work explores whether and how deference to people’s choices might be reconciled with behavioral findings about human error. This work has strong implications for economic analysis of law, cost–benefit analysis, and regulatory policy. In light of behavioral findings, regulators should adopt a working presumption in favor of respect for people’s self-regarding choices, but only if those choices are adequately informed and sufficiently free from behavioral biases. The working presumption should itself be rebuttable on welfare grounds, with an understanding that the ends that people choose might make their lives go less well. For example, people might die prematurely or suffer from serious illness, and what they receive in return might not (on any plausible account of welfare) be nearly enough. The underlying reason might involve a lack of information or a behavioral bias, identifiable or not, in which case intervention can fit with the working presumption, but the real problem might involve philosophical questions about the proper understanding of welfare, and about what it means for people to have a good life.

negative: The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation Abstract The 2–5A system is an RNA degradation pathway that can be induced by the interferons (IFNs). Treatment of cells with IFN activates genes encoding several double-stranded RNA (dsRNA)-dependent synthetases. These enzymes generate 5′-triphosphorylated, 2′,5′-phosphodiester-linked oligoadenylates (2–5A) from ATP. The effects of 2–5A in cells are transient since 2–5A is unstable in cells due to the activities of phosphodiesterase and phosphatase. 2–5A activates the endoribonuclease 2–5A-dependent RNase L, causing degradation of single-stranded RNA with moderate specificity. The human 2–5A-dependent RNase is an 83.5 kDa polypeptide that has little, if any, RNase activity, unless 2–5A is present. 2–5A binding to RNase L switches the enzyme from its off-state to its on-state. At least three 2′,5′-linked oligoadenylates and a single 5′-phosphoryl group are required for maximal activation of the RNase. Even though the constitutive presence of 2–5A-dependent RNase is observed in nearly all mammalian cell types, cellular amounts of 2–5A-dependent mRNA and activity can increase after IFN treatment. One well-established role of the 2–5A system is as a host defense against some types of viruses. Since virus infection of cells results in the production and secretion of IFNs, and since dsRNA is both a frequent product of virus infection and an activator of 2–5A synthesis, the replication of encephalomyocarditis virus, which produces dsRNA during its life cycle, is greatly suppressed in IFN-treated cells as a direct result of RNA decay by the activated 2–5A-clependent RNase. This review covers the organic chemistry, enzymology, and molecular biology of 2–5A and its associated enzymes. Additional possible biological roles of the 2–5A system, such as in cell growth and differentiation, human immunodeficiency virus replication, heat shock, atherosclerotic plaque, pathogenesis of Type I diabetes, and apoptosis, are presented.

negative: The socio-economic determinants of the coronavirus disease (COVID-19) pandemic The magnitude of the coronavirus disease (COVID-19) pandemic has an enormous impact on the social life and the economic activities in almost every country in the world. Besides the biological and epidemiological factors, a multitude of social and economic criteria also govern the extent of the coronavirus disease spread in the population. Consequently, there is an active debate regarding the critical socio-economic determinants that contribute to the resulting pandemic. In this paper, we contribute towards the resolution of the debate by leveraging Bayesian model averaging techniques and country level data to investigate the potential of 35 determinants, describing a diverse set of socio-economic characteristics, in explaining the coronavirus pandemic outcome.

negative: Analysis of Effectiveness of Quarantine Measures in Controlling COVID-19 COVID-19 has created an interesting discourse among the people of the world particularly regarding preventive measures of infectious diseases. In this paper, the authors forecast the spread of the Corona virus outbreak and study how the reduction of transmission rates influences its decline. The paper makes use of the SIR (Susceptible Infected Recovered) Model which is a deterministic model used in the field of epidemiology-based on differential equations derived from sections of the population. The Basic Reproduction Number (Ro) represents the criticality of the epidemic in numeric terms. Forecasting an epidemic provides insights about the geographic spreading of the disease and the case incidences required to better inform intervention strategists about situations that may occur during the outbreak. Through this research paper, the authors wish to provide an insight into the impact of control measures on the pandemic. By drawing a comparison of three countries and their quarantine measures, observations on the decline of the outbreak are made. Authors intend to guide the intervention strategies of under-resourced countries like India and aid in the overall containment of the outbreak.

negative: Anxiety, worry and perceived stress in the world due to the COVID-19 pandemic, March 2020. Preliminary results. Introduction: Since the beginning of the outbreak in China, ending 2019, the Novel Coronavirus (COVID-19) has spread subsequently to the rest of the world causing an on-going pandemic. The World Health Organisation (WHO) declared COVID-19: a public health emergency of international concern. Having into consideration the lockdown and quarantine situation, we decided to do evaluate the current emotional state on the general population with a web-based survey in English and in Spanish, which was considered a useful and fast method that could help us determine how people perceived stress and worry due to the COVID-19. Methods: The survey included a 22 items, gathering information in 3 sections: Sociodemographic data, the Perceived Stress Scale (PSS-10) by Cohen and additional queries that assessed the current worry and change of behaviours due to this pandemic. Results: The survey received 891 respondents from 25 countries, from March 17 to 23rd, 2020. The mean age of the respondents was 43.8 (14.2) years old, and more than two thirds were women. 12.8% were health personnel.The mean of the PSS-10 score was 17.4 (6.4). Significantly higher scores were observed among women, youth, students, and among those who expressed concern and those who perceived increased susceptibility to the COVID-19. In contrast, no significant differences were observed between the health professionals and the general population. A good correlation was observed between mean relative volume (RSV) of the las 14 days and the number of cases reported (rho = 0.68, p <0.001) and deaths (rho = 0.51, p <0.001). Discussion: With these results we describe an increase of affective symptoms due to the COVID-19. This pandemic is raising the anxiety levels. The findings of our study show the affective and cognitive alterations people are going through. This survey is the first attempt to measure the psychological consequences this pandemic is having, in order to be able to later be able to provide the support to confront this global issue, addressing the mental health care that will be needed.

negative: Chapter 4 Communicable Diseases Abstract Sanitation, food control, vaccines, and antibiotics have reduced the toll of communicable diseases, saving millions of lives. Smallpox was eradicated in 1977, and poliomyelitis eradication is close. Measles mortality has reduced drastically yet outbreaks occur where immunization lags. HIV/AIDS emerged in the 1980s, grew into a global pandemic costing millions of lives, and despite progress remains a major global health issue. Malaria and tuberculosis still cause millions of deaths. Influenza pandemics with new, deadly versions continue to appear. Neglected tropical diseases are responding to global donor efforts. Newly emerging diseases move to new regions and became endemic, and deadly localized hemorrhagic fevers threaten to transmit more widely. Rapid mass travel allows infectious diseases in isolated villages to quickly become global threats. New strains of viruses, antibiotic resistance, and microorganisms causing chronic diseases are challenges for infectious disease control requiring continuing political, financial, and scientific support, and much tenacity.

negative: Covid-19: Adapting the geriatric organisations to respond to the pandemic

negative: An empirical estimate of the infection fatality rate of COVID-19 from the first Italian outbreak Background: The coronavirus 2019 (COVID-19) pandemic has been spread-ing globally for months, yet the infection fatality ratio of the disease is still uncertain. This is partly because of inconsistencies in testing and death reporting standards across countries. Our purpose is to provide accurate estimates which do not rely on testing and death count data directly but only use population level statistics. Methods: We collected demographic and death records data from the Italian Institute of Statistics. We focus on the area in Italy that experienced the initial outbreak of COVID-19 and estimated a Bayesian model fitting age-stratified mortality data from 2020 and previous years. We also assessed the sensitivity of our estimates to alternative assumptions on the proportion of population infected. Findings: We estimate an overall infection fatality rate of 1.29% (95% credible interval [CrI] 0.89 - 2.01), as well as large differences by age, with a low infection fatality rate of 0.05% for under 60 year old (CrI 0-.19) and a substantially higher 4.25% (CrI 3.01-6.39) for people above 60 years of age. In our sensitivity analysis, we found that even under extreme assumptions, our method delivered useful information. For instance, even if only 10% of the population were infected, the infection fatality rate would not rise above 0.2% for people under 60. Interpretation: Our empirical estimates based on population level data show a sharp difference in fatality rates between young and old people and firmly rule out overall fatality ratios below 0.5% in populations with more than 30% over 60 years old.

negative: Forecast of the COVID-19 outbreak, collapse of medical facilities, and lockdown effects in Tokyo, Japan Background: The number of patients of COVID-19 in Tokyo has been increasing gradually through the end of March, 2020. Object: Support for policymaking requires forecasting of the entire course and outcome of the outbreak including the date of collapse of medical facilities if a lockdown is not initiated. Moreover, the effects of a lockdown must be considered when choosing to initiate one. Method: Data of Tokyo patients with symptoms during January 14 − March 28, 2020 were used to formulate a susceptible−infected−recovered (SIR) model using three age classes and to estimate the basic reproduction number (R0). Based on the estimated R0, We inferred outbreak outcomes including the date of collapse of medical facilities if a lockdown were not enacted. Then we estimate the lockdown effects. Results: Results suggest R0 as 2.86, with a 95% confidence interval of [2.73, 2.97]. Collapse of medical facilities can be expected to occur on April 26 if no lockdown occurs. The total number of deaths can be expected to be half a million people. If a lockdown were enacted from April 6, and if more than 60% of trips outside the home were restricted voluntarily, then a collapse of medical facilities could be avoided. Discussion and Conclusion: The estimated R0 was similar to that found from other studies conducted in China and Japan. Results demonstrate that a lockdown with reasonable cooperation of residents can avoid a collapse of medical facilities and save 0.25 million mortality cases.

negative: How villagers in central Sierra Leone understand infection risks under threat of Covid-19 BACKGROUND: Concern has been expressed over how well Africa is prepared to cope with the pandemic of Covid-19. Will rural populations with low levels of education know how to apply community-based infection control? We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. METHODS: Two communities were selected based on prior contrasted exposure to Ebola Virus Disease–one with substantial number of cases and the other having resisted infection through strong community sequestration measures. We assessed understanding of infection risks via an experimental game. This asked players to express a preference for one of two diseases, one resembling Ebola with lower risk of infection and the other resembling Covid-19 with lower risk of death. Players were not told the identity of the diseases. RESULTS: In total 107 adult villagers played the game (58% women). Half (52%) preferred the disease model with lower risk of infection, 29% preferred the model with lower risk of death, while 21% saw the combined risk of infection and death as being equivalent. Differences in reactions between the two locations were small despite different experiences of Ebola. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. We concluded that villagers thoughtfully assess disease risks and that some are good intuitive statisticians. CONCLUSIONS: Results suggest rural people in Sierra Leone retain the lessons of experience from the Ebola outbreak of 2014–15 and will be able to apply these lessons to a new infectious disease for which have no prior practical experience. Our expectation is that rural populations will understand Covid-19 control measures, thus reducing need for draconian enforcement.

negative: Real estimates of mortality following COVID-19 infection

negative: A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruses World Health Organization has declared the ongoing outbreak of coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern. The virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. Human infection with SARS-CoV-2 leads to a wide range of clinical manifestations ranging from asymptomatic, mild, moderate to severe. The severe cases present with pneumonia, which can progress to acute respiratory distress syndrome. The outbreak provides an opportunity for real-time tracking of an animal coronavirus that has just crossed species barrier to infect humans. The outcome of SARS-CoV-2 infection is largely determined by virus-host interaction. Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defense. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes. Important questions concerning the interaction between SARS-CoV-2 and host antiviral defence, including asymptomatic and presymptomatic virus shedding, are also discussed.

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: Specific ACE2 Expression in Small Intestinal Enterocytes may Cause Gastrointestinal Symptoms and Injury after 2019-nCoV Infection Abstract The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients’ stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.

negative: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. OBJECTIVE: To estimate the length of the incubation period of COVID-19 and describe its public health implications. DESIGN: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. SETTING: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. PARTICIPANTS: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. MEASUREMENTS: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. RESULTS: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. LIMITATION: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. CONCLUSION: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. PRIMARY FUNDING SOURCE: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.

negative: South Africa hopes its battle with HIV and TB helped prepare it for COVID-19 As the COVID-19 pandemic sweeps into South Africa, the decades the country has spent fighting the world’s worst combined epidemic of tuberculosis (TB) and HIV could give it an advantage But those infections could also worsen the pandemic’s impact By 6 April, South Africa had 1686 confirmed COVID-19 infections, the highest number on the continent—and that is almost certainly an undercount At the same time, one in every five people aged 15 to 49 is HIV positive and two to three people die every hour from TB South African scientists hope the resources and health networks built to fight those diseases will help them battle the new pandemic “The COVID-19 response draws on the same skills as TB and HIV,” says Gavin Churchyard, director of the Aurum Institute, a Johannesburg-based research and health care nonprofit

negative: Herd immunity or suppression strategy to combat COVID-19. Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called "herd immunity" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden.Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants).In the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state Taiwan has made the best out of the pandemic situation whereas Sweden failed completely.

negative: The COVID-19 Pandemic in Japan Since its initial outbreak in China, in December, 2019, COVID-19 has spread rapidly across the globe. At the time of writing, on April 29, 2020, infections had been confirmed in more than 200 countries and regions and 3,018,681 infections and 207,973 deaths had been recorded. In Japan, the first confirmed case of SARS-CoV-2 infection was reported on January 16, 2020, since when, the number of domestic infections and the death toll have reached 13,852 and 389, respectively, representing exponential increases. Moreover, both domestically and internationally, the shortage of medical resources and the spread of infection among medical personnel, caused by nosocomial transmissions have become problematic. The pathology of COVID-19, including the exact infection route, remains largely unknown. Given the unavailability of an effective cure and vaccine, people are required to respond to this adversity without becoming complacent. The global efforts against the COVID-19 pandemic are ongoing endeavors, far from over. New epidemiological data and clinical findings are emerging on a daily basis, making it critical to always refer to the latest information.

negative: Analysis of the Worldwide Corona Virus (COVID-19) Pandemic Trend;A Modelling Study to Predict Its Spread Objective: The Coronavirus (COVID-19) has advanced into 197 countries and territories leaving behind a total of 372,757 confirmed cases and 16231 deaths. Methods: One the basis of WHO situation reports data of COVID-19 along with daily official reports from the Japan, China and the Korea we modeled the spread of COVID19 by using the Successive Approximation Method. We defined the two state of data to find the mean ratio (η) of the present cases count to the sum of previous and present cases. This ratio further predicts the future state of COVID-19 pandemic. Results: The mean ratio (η) of expected cases were found 0.485, while the mean ratio for deaths was found to be 0.49. We calculated worldwide expected lower bound value for confirmed cases 247007 cases with maximum limit of 1667719 cases and minimum deaths count 8660 with upper limit of 117397 deaths in next 30 days. While in the case of Iran, a large increase in the number of deaths are expected in the upcoming 30 days with lower bound value of 1140 deaths and maximum value of 598478 deaths. Interpretation: Iran whole population is on risk.

negative: Emerging infections and their causative agents

negative: Discovering drugs to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.

negative: Hajj-associated infections Abstract Background The Hajj is the largest annual mass gathering event in the world, thus favoring the transmission of various infections: 183 different nationalities, high temperatures, coincidence with the start of the flu season in the Northern hemisphere, a long barefoot walk, tent-type accommodation, communal toilet facilities, absence of food control, and sharing of razors. Infections are the first cause of hospital admission, which often occurs in the home country of pilgrims. Methods Literature review on PubMed from 1952 to November 2015 on the epidemiology and prevention of infections contracted during the Hajj, using the keywords “Hajj” and “infections”. Results Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj. Outbreaks of meningococcal meningitis have been reported in pilgrims and their contacts. Waterborne infections such as gastroenteritis and hepatitis A are common, despite the improvement of health conditions. Pyoderma and furuncles are also frequently observed. Recently, dengue fever, Alkhumra hemorrhagic fever, and Rift Valley fever have emerged but no case of MERS-coronavirus, appeared in Saudi Arabia in 2012, have yet been observed during the 2012–2014 Hajj. Conclusion Prevention is based on compulsory meningococcal vaccination, vaccination against seasonal influenza and pneumococcal infections for pilgrims at high risk of contracting the infection, and on vaccination against hepatitis A. Updating immunization for diphtheria/tetanus/poliomyelitis/pertussis and measles/mumps is also crucial and pilgrims must comply with hygiene precautions.

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: 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: Advanced Pathology Techniques for Detecting Emerging Infectious Disease Pathogens The control and prevention of infectious diseases remain a fundamental part of public health programs throughout the world. The modern medicine and public health have been challenged by a series of emerging and reemerging infections in the past three decades. These diseases have occurred following a false sense of victory over infectious diseases on a global scale due to effective vaccinations and antibiotic agents against certain microorganisms. Because of the unique circumstances of the modern world, these new infectious diseases are emerging at much faster rates than before, and old ones are returning with formidable strength. These infections have posed severe threats to global public health and have raised serious questions regarding the capability of modern medicine to face their challenges. Therefore, it is crucial to understand the dynamics and impact of these emerging and reemerging infectious diseases. Diagnostic pathology continues to be an essential counterpart of clinical microbiology in dealing with emerging and reemerging infections. Diagnosis with advanced pathology techniques not only helps identify or confirm the novel pathogens causing emerging infections but is also essential for epidemiologic surveillance and studying pathogenesis of these emerging infections.

negative: Achievements and highlights for Infection, Disease and Health

negative: A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.

negative: Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses Abstract A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.

negative: Answering the initial 20 questions on COVID-19 (January-February 2020)

negative: Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase Background Coronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC). Method Using the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020. Results Using spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters. Conclusion Compared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.

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: How long do nosocomial pathogens persist on inanimate surfaces? A systematic review BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.

negative: The Imperfect Cytokine Storm: Severe COVID-19 with ARDS in Patient on Durable LVAD Support Abstract As health systems worldwide grapple with the COVID-19 pandemic, patients on durable LVAD support represent a unique population at risk for the disease. We outline such a patient who developed COVID-19 complicated by “cytokine storm” with severe ARDS and myocardial injury; and describe the challenges that arose during management.

negative: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. Importance Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results There were approximately 781 000 total deaths in the United States from March 1 to May 30, 2020, representing 122 300 (95% prediction interval, 116 800-127 000) more deaths than would typically be expected at that time of year. There were 95 235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

negative: Pre-outbreak determinants of perceived risks of corona infection and preventive measures taken. A prospective population-based study Objectives. Assess how people perceive the risks of coronavirus infection, whether people take preventive measures, and which (pre-outbreak) factors contribute to the perceived risks and measures taken, such as (pre-outbreak) respiratory problems, heart problems, diabetes, anxiety and depression symptoms, loneliness, age, gender, marital status and education level. Methods. Data were collected in the longitudinal LISS panel, based on a random sample of the Dutch population. The coronavirus survey started on March 2, and the data collection ended on March 17 2020. Data were linked with surveys on health and social integration conducted at the end of 2019 (Nstudy sample=3,540). Results. About 15% perceived the risk of infection as high, and 11% the risk becoming ill when infected. Multivariate logistic regression analyses showed the following. Older age-groups perceived the risk for coronavirus infection as lower (all adjusted Odd Ratios [aOR] smaller than .058). In total, 43.8% had taken preventive measures, especially females (aOR=1.47, 95% CI=1.27-1.69). Those with lower education levels less often used preventive measures (aOR=0.56, 95% CI=0.46-0.69). Those with pre-outbreak respiratory problems (aOR=2.89, 95% CI=2.24-3.73), heart problems (aOR=2.17, 95% CI=1.49-3.16) and diabetes (aOR=3.10, 95% CI=2.02-4.74) perceived the risk becoming ill when infected as higher than others. However, respondents with pre-outbreak respiratory problems and diabetes did not more often take preventive measures. Conclusions. Vulnerable patients more often recognize that they are at risk becoming ill when infected by the coronavirus, but many do not take preventive measures. Interventions to stimulate the use of preventive measures should pay additional attention to physically vulnerable patients, men and those with lower education levels.

negative: Characteristics of health worker fatality in China during the outbreak of COVID-19 infection

negative: “Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.” BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I(2) statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I(2) = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I(2) = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.

negative: Comprehensive Identification and Isolation Policies Have Effectively Suppressed the Spread of COVID-19 The outbreak of COVID-19 has caused severe life and economic damage worldwide. Since the absence of medical resources or targeted therapeutics, systemic containment policies have been prioritized but some critics query what extent can they mitigate this pandemic. We construct a fine-grained transmission dynamics model to forecast the crucial information of public concern, therein using dynamical coefficients to quantify the impact of the implement schedule and intensity of the containment policies on the spread of epidemic. Statistical evidences show the comprehensive identification and quarantine policies eminently contributed to reduce casualties during the phase of a dramatic increase in diagnosed cases in Wuhan and postponing or weakening such policies would undoubtedly exacerbate the epidemic. Hence we suggest that governments should swiftly execute the forceful public health interventions in the initial stage until the pandemic is blocked.

negative: Swine acute diarrhea syndrome coronavirus-induced apoptosis is caspase- and cyclophilin D- dependent Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the aetiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. To understand the effect of SADS-CoV on host cells, we characterized the apoptotic pathways and elucidated mechanisms underlying the process of apoptotic cell death after SADS-CoV infection. SADS-CoV-infected cells showed evidence of apoptosis in vitro and in vivo. The use of a pan-caspase inhibitor resulted in the inhibition of SADS-CoV-induced apoptosis and reduction in SADS-CoV replication, suggestive of the association of a caspase-dependent pathway. Furthermore, SADS-CoV infection activated the initiators caspase-8 and -9 and upregulated FasL and Bid cleavage, demonstrating a crosstalk between the extrinsic and intrinsic pathways. However, the proapoptotic proteins Bax and Cytochrome c (Cyt c) relocalized to the mitochondria and cytoplasm, respectively, after infection by SADS-CoV. Moreover, Vero E6 and IPI-2I cells treated with cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP) opening, were completely protected from SADS-CoV-induced apoptosis and viral replication, suggesting the involvement of cyclophilin D (CypD) in these processes. Altogether, our results indicate that caspase-dependent FasL (extrinsic)- and mitochondria (intrinsic)- mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis that facilitates viral replication. In summary, these findings demonstrate mechanisms by which SADS-CoV induces apoptosis and improve our understanding of SADS-CoV pathogenesis.

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: COVID-19: Estimating spread in Spain solving an inverse problem with a probabilistic model We introduce a new probabilistic model to estimate the real spread of the novel SARS-CoV-2 virus along regions or countries. Our model simulates the behavior of each individual in a population according to a probabilistic model through an inverse problem; we estimate the real number of recovered and infected people using mortality records. In addition, the model is dynamic in the sense that it takes into account the policy measures introduced when we solve the inverse problem. The results obtained in Spain have particular practical relevance: the number of infected individuals can be $17$ times higher than the data provided by the Spanish government on April $26$ $th$ in the worst-case scenario. Assuming that the number of fatalities reflected in the statistics is correct, $9.8$ percent of the population may be contaminated or have already been recovered from the virus in Madrid, one of the most affected regions in Spain. However, if we assume that the number of fatalities is twice as high as the official numbers, the number of infections could have reached $19.5\%$. In Galicia, one of the regions where the effect has been the least, the number of infections does not reach $2.5 \%$ . Based on our findings, we can: i) estimate the risk of a new outbreak before Autumn if we lift the quarantine; ii) may know the degree of immunization of the population in each region; and iii) forecast or simulate the effect of the policies to be introduced in the future based on the number of infected or recovered individuals in the population.

negative: Recent Understandings Toward Coronavirus Disease 2019 (COVID-19): From Bench to Bedside In late December 2019, an unprecedented outbreak of coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2) (previously named 2019-nCoV) in Wuhan became the most challenging health emergency. Since its rapid spread in China and many other countries, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern (PHEIC) on 30th January 2020 and a pandemic on 11th March 2020. Thousands of people have died, and there are currently no vaccines or specific antiviral drugs for COVID-19. Therefore, it is critical to have a comprehensive understanding of the virus. In this review, we highlight the etiology, epidemiology, pathogenesis and pathology, clinical characteristics, diagnosis, clinical management, prognosis, infection control and prevention of COVID-19 based on recent studies.

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: Novel coronavirus, poor quarantine, and the risk of pandemic

negative: Special considerations for the management of COVID-19 pediatric patients in the operating room and pediatric intensive care unit in a tertiary hospital in Singapore COVID-19 was first identified in Wuhan, China and is caused by the novel coronavirus SARS-CoV 2. It has now spread rapidly to over 190 countries and territories around the world and has been declared a global pandemic by the World Health Organization. The virus is spread through droplet transmission and currently has a mortality rate of over 4% globally. The pediatric population has been found to be less susceptible to the disease with the majority of children having milder symptoms and only one pediatric death being reported globally so far. Despite this, strategies need to be put in place to prevent further spread of the virus. We present a summary of the general measures implemented at a large adult and pediatric tertiary hospital in Singapore (National University Hospital) as well as the specific strategies in place for the operating room and pediatric intensive care unit.

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: Antimikrobielle und antiinfektiöse Maßnahmen

negative: An SEIR Model for Assessment of Current COVID-19 Pandemic Situation in the UK The ongoing COVID-19 pandemic spread to the UK in early 2020 with the first few cases being identified in late January. A rapid increase in confirmed cases started in March, and the number of infected people is however unknown, largely due to the rather limited testing scale. A number of reports published so far reveal that the COVID-19 has long incubation period, high fatality ratio and non-specific symptoms, making this novel coronavirus far different from common seasonal influenza. In this note, we present a modified SEIR model which takes into account the time lag effect and probability distribution of model states. Based on the proposed model, it is estimated that the actual total number of infected people by 1 April in the UK might have already exceeded 610,000. Average fatality rates under different assumptions at the beginning of April 2020 are also estimated. Our model also reveals that the R0 value is between 7.5-9 which is much larger than most of the previously reported values. The proposed model has a potential to be used for assessing future epidemic situations under different intervention strategies.

negative: Toll of acute methanol poisoning for preventing COVID-19

negative: Evaluation of the US governors decision when to issue stay-at-home orders Objectives To evaluate if the US governors decision to issue the stay-at-home orders reflects the classic Weber-Fechner law of psychophysics, the amount by which a stimulus (such as number of cases or deaths) must increase in order to be noticed-the just noticeable difference- as a fraction of the intensity of that stimulus. Design A prospective observational study using data on the daily number of infected patients and deaths from the New York Times daily database. Setting 50 States and the District of Columbia Participants All individuals judged to be positive for the coronavirus or to have died from COVID19. Main outcome measures Number of people diagnosed with or died from COVID19. Results We found that the decision to issue the state-at-home order reflects the Weber-Fechner law of psychophysics. Both the number of infections (p=<0.0001; R2=0.79) and deaths (p<0.0001; R2=0.63) were highly statistically significantly associated with the decision to issue the stay-at-home orders. The results indicate that for each doubling of infections or deaths within their state, an additional four to six governors will issue the stay-at-home order. We also observed a clear dose-response relationship in the Cox model: the larger the number of cases, or deaths, the higher the probability that the stay-at-home order will be made. When the number of deaths reached 256 or the number of infected people was greater than 16,384, the probability of issuing a stay-at-home order was close to 100%. Conclusions When there are not clearly articulated rules to follow, decision-makers in times of crisis such as COVID19 resort to use of simple heuristics consistent with the Weber-Fechner law of psychophysics. The findings are important for the public to understand how their elected officials make important public health decisions.

negative: [Management and clinical thinking of Coronavirus Disease 2019]. In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.

negative: Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings OBJECTIVES: The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. METHODS: Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. RESULTS: The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. CONCLUSIONS: Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.

negative: Respiratory viruses and cot death. Respiratory viruses and histological appearances of the lung were studied prospectively in an unselected series of 104 children who died between 1 week and 2 years of age. Thirty-one of the cases were cot deaths. Seven of these showed evidence of active virus infection in the lower respiratory tract. Similar evidence was found in two children who died from known causes and did not have a severe respiratory illness terminally. Although in some cases of cot death respiratory viruses may be responsible for a severe and rapidly overwhelming illness, the present results are compatible with an alternative hypothesis-namely, that minor respiratory illness may trigger sudden apnoea.

negative: Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.

negative: COVID-19 infection and rheumatoid arthritis: Faraway, so close! Abstract The outbreak of the new coronavirus infections COVID-19 in December 2019 in China has quickly become a global health emergency. Given the lack of specific anti-viral therapies, the current management of severe acute respiratory syndrome coronaviruses (SARS-CoV-2) is mainly supportive, even though several compounds are now under investigation for the treatment of this life-threatening disease. COVID-19 pandemic is certainly conditioning the treatment strategy of a complex disorder as rheumatoid arthritis (RA), whose infectious risk is increased compared to the general population because of an overall impairment of immune system typical of autoimmune diseases combined with the iatrogenic effect generated by corticosteroids and immunosuppressive drugs. However, the increasing knowledge about the pathophysiology of SARS-CoV-2 infection is leading to consider some anti-rheumatic drugs as potential treatment options for the management of COVID-19. In this review we will critically analyse the evidences on either positive or negative effect of drugs commonly used to treat RA in this particular scenario, in order to optimize the current approach to RA patients.

negative: Likelihood of survival of coronavirus disease 2019

negative: Systematic review of international guidelines for tracheostomy in COVID-19 patients. At this moment, the world leaves under the SARS-CoV-2 outbreak pandemic. As Otolaryngologists - Head & Neck Surgeons, we need to perform and participate in examinations and procedures within the head and neck region and airway that are at particularly high risk of exposure and infection because of aerosol and droplet contamination. One of those surgical procedures on demand at this moment is tracheostomy, due the increasing admission in ICU departments and the increased need of ventilatory support secondary to respiratory distress syndrome. This review of international guidelines for tracheostomy in COVID-19 infected patients, aiming to summarize in a systematic way the available recommendations from 18 guidelines from all over the world.

negative: [What to do about the deceased in suspected, probable and confirmed COVID-19 cases]. The SARS-CoV-2 beta-coronavirus outbreak, which first appeared in Wuhan, China, in late 2019, was declared a pandemic by the World Health Organization on March 11, 2020. The first confirmed case of COVID-19 was reported in Hungary on 4 March 2020, and the first patient infected with a new type of coronavirus died on 15 March. At the time of the deceased's death, there was no central, uniform directive clarifying the range of precautions required or providing a clear description of the safe handling of the corpse. Transporting the dead to a pathology department, storing them, possibly dissecting them, and then placing them in their final resting place, how these raise countless questions. The current legislation on communicable diseases and actions on the dead does not provide sufficient information on the performance of tasks after the death of a COVID-19 infected patient. On March 19, the national chief medical officer suspended the autopsies, except for forensic autopsies, but transportation and storage remained a problem. Although on March 21, 2020, the Department of Pathology of the Health Professional College of the Ministry of Human Resources issued a formal procedure, the recommendations contained therein represent a narrower spectrum of literature and need to be supplemented in several places. Unfortunately, data on post-mortem procedures are also under-represented in the international literature, given their importance. Another problem is that in the articles written for the treatment of the victims of crisis situations caused by epidemics, the available algorithms take into account different organizational and resource possibilities in addition to the legal environment different from Hungary, which circumstances make domestic adaptation significantly more difficult. In our article, in addition to the literature review, we formulate suggestions and recommendations for healthcare professionals involved in the treatment of COVID-19 suspected, probable and confirmed patients, as well as potentially affected pathology departments, which increase the safety of providers. * Orv Hetil. 2020; 161 (17): 713-722.

negative: COVID-19 Blockchain Framework: Innovative Approach The world is currently witnessing dangerous shifts in the epidemic of emerging SARS-CoV-2, the causative agent of (COVID-19) coronavirus. The infection, and death numbers reported by World Health Organization (WHO) about this epidemic forecasts an increasing threats to the lives of people and the economics of countries. The greatest challenge that most governments are currently suffering from is the lack of a precise mechanism to detect unknown infected cases and predict the infection risk of COVID-19 virus. In response to mitigate this challenge, this study proposes a novel innovative approach for mitigating big challenges of (COVID-19) coronavirus propagation and contagion. This study propose a blockchain-based framework which investigate the possibility of utilizing peer-to peer, time stamping, and decentralized storage advantages of blockchain to build a new system for verifying and detecting the unknown infected cases of COVID-19 virus. Moreover, the proposed framework will enable the citizens to predict the infection risk of COVID-19 virus within conglomerates of people or within public places through a novel design of P2P-Mobile Application. The proposed approach is forecasted to produce an effective system able to support governments, health authorities, and citizens to take critical decision regarding the infection detection, infection prediction, and infection avoidance. The framework is currently being developed and implemented as a new system consists of four components, Infection Verifier Subsystem, Blockchain platform, P2P-Mobile Application, and Mass-Surveillance System. This four components work together for detecting the unknown infected cases and predicting and estimating the infection Risk of Corona Virus (COVID-19).

negative: A systems approach to natural disaster resilience Abstract The frequency, social, and economic impacts of natural disasters show exponential increases in recent decades. Cities and countries around the world have begun to realize that these events are no longer “hundred year” storms, but repeat within a few years. As urbanisation continues throughout this century, more and more people and more economic activity will be concentrated in at-risk areas; especially as new arrivals in cities throughout Asia and Africa are likely to be concentrated in the highest risk districts, much as they often are in North America and Europe today. This article reviews recent growth of natural disasters and considers how a systems approach can improve approaches to mitigation and adaptation of these risks and to recovery from such events.

negative: Inactivation of murine norovirus on a range of copper alloy surfaces is accompanied by loss of capsid integrity. Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via the fecal-oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus. In this study, a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials, including Teflon (polytetrafluoroethylene [PTFE]), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. Persistence was slightly prolonged on ceramic surfaces. A previous study in our laboratory observed that dry copper and copper alloy surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study, we have observed that a relatively small change in the percentage of copper, between 70 and 80% in copper nickels and 60 and 70% in brasses, had a significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus, but zinc did have some antiviral effect, which was synergistic with copper and resulted in an increased efficacy of brasses with lower percentages of copper. Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested that a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests that capsid integrity is compromised upon contact with copper, allowing copper ion access to the viral genome.

negative: Covid-19: death rate is 0.66% and increases with age, study estimates

negative: Analysis of the evolution of the Sars-Cov-2 in Italy, the role of the asymptomatics and the success of Logistic model In this letter we study the temporal evolution of the Sars-Cov-2 in Italy. The time window of the real data is between February 24 and March 25. After we upgrade the data until April 1.We perform the analysis with 4 different model and we think that the best candidate to describe correctly the italian situation is a generalized Logistic equation. We use two coupled differential equations that describe the evolution of the severe infected and the deaths. We have done this choice, because in Italy the pharyngeal swabs are made only to severe infected and so we have no information about asymptomatic people. An important observation is that the virus spreads between Regions with some delay; so we suggest that a different analysis region by region would be more sensible than that on the whole Italy. In particular the region Lombardia has a behaviour very fast with respect to the other ones. We show the behaviour of the total deaths and the total severe infected for Italy and five regions: Lombardia, Emilia Romagna, Veneto, Piemonte, Toscana. Finally we do an analysis of the peak and an estimation of how many lifes have been saved with the LockDown.

negative: Heat-Related Deaths — United States, 2004–2018 Deaths attributable to natural heat exposure, although generally considered preventable (1), represent a continuing public health concern in the United States. During 2004-2018, an average of 702 heat-related deaths occurred in the United States annually. To study patterns in heat-related deaths by age group, sex, race/ethnicity, and level of urbanization, and to explore comorbid conditions associated with deaths resulting from heat exposure, CDC analyzed nationally comprehensive mortality data from the National Vital Statistics System (NVSS).* The rate of heat-related mortality tended to be higher among males, persons aged ≥65 years, non-Hispanic American Indian/Alaska Natives, and persons living in noncore nonmetropolitan and large central metropolitan counties. Natural heat exposure was a contributing cause of deaths attributed to certain chronic medical conditions and other external causes. Preparedness and response initiatives directed toward extreme heat events, currently underway at local, state, and national levels, can contribute to reducing morbidity and mortality associated with natural heat exposure. Successful public health interventions† to mitigate heat-related deaths include conducting outreach to vulnerable communities to increase awareness of heat-related symptoms and provide guidance for staying cool and hydrated, particularly for susceptible groups at risk such as young athletes and persons who are older or socially isolated (2). Improved coordination across various health care sectors could inform local activities to protect health during periods of high heat. For instance, jurisdictions can monitor weather conditions and syndromic surveillance data to guide timing of risk communication and other measures (e.g., developing and implementing heat response plans, facilitating communication and education activities) to prevent heat-related mortality in the United States. CDC also recommends that federal, state, local, and tribal jurisdictions open cooling centers or provide access to public locations with air conditioning for persons in need of a safe, cool, environment during hot weather conditions. In light of the coronavirus disease 2019 (COVID-19) pandemic, CDC updated its guidance on the use of cooling centers to provide best practices (e.g., potential changes to staffing procedures, separate areas for persons with symptoms of COVID-19, and physical distancing) to reduce the risk for introducing and transmitting SARS COV-2, the virus that causes COVID-19, into cooling centers.§.

negative: Autismus und Autismustherapie in Zeiten von Corona: eine Chance? The worldwide coronavirus crisis represents for each of us a new, unexpected, and particularly challenging situation, and is accompanied by strong emotions of fear and insecurity in people with and without autism. The measures initiated range from distancing and hygiene regulations through to a reduced social life. This article deals with the impact of this new situation on people with autism and on autism therapy. In addition to the description of positive effects on people with autism, current therapeutic developments and interventions during the coronavirus pandemic form the focus of this paper.

negative: QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.

negative: COVID-19 presenting as acute pancreatitis The ongoing pandemic of Coronavirus disease-2019 (COVID-19) has spread over 200 countries worldwide, affecting >2 million people and >120,000 deaths. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most common symptoms include cough, shortness of breath, and fever. However, gastrointestinal manifestations of COVID-19 are increasingly being recognized. Herein, we report a case of COVID-19 who presented with acute pancreatitis (AP) without any other risk factors.

negative: Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International Concern. However, so far, there are still controversies about the source of the virus and its intermediate host. Here, we found the novel coronavirus was closely related to coronaviruses derived from five wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, and was in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as the coronavirus derived from these five animals, whereas the virus has the highest homology with Bat coronavirus isolate RaTG13.

negative: Predicting clinical needs derived from the COVID-19 pandemic: the case of Spain Background The evolution of the pandemic caused by COVID-19, its high reproductive number and the associated clinical needs, is overwhelming national health systems. We propose a method for predicting both ICU requirements and the number of deaths, and which will enable the health authorities of the countries involved to plan the resources needed to face the pandemic as many days in advance as possible. Methods We use official Spanish data to predict ICU admissions and deaths based on the number of infections. We employ OLS to perform the econometric estimation, and through RMSE, MSE, MAPE, and SMAPE forecast performance measures we select the best lagged predictor of both dependent variables. Findings For Spain, our prediction shows that the best predictor of ICU admissions is the number of people infected eight days before, and that the best predictor of deaths is the number of people infected five days before. In the first case, we obtain a 98% coefficient of determination, and in the second a 97% coefficient. The estimated delayed elasticities find that a 1% increase in the number of cases today will imply a 0.72% increase in ICU patients eight days later and a 1.09% increase in the number of deaths five days later. Interpretation The model is not intended to analyse the epidemiology of COVID-19. Our objective is rather to estimate a leading indicator of clinical needs. Having a forecast model available several days in advance can enable governments to more effectively face the gap between needs and resources triggered by the outbreak and thus reduce the deaths caused by COVID-19.

negative: Bewegung und Erkrankungen des Immunsystems Die Effektivität von körperlicher Aktivität in der Primär- als auch Sekundär- und Tertiärprävention ist hinlänglich bekannt. Das Immunsystem spielt eine entscheidende Rolle bei einer Vielzahl von Erkrankungen, da es durch seine Botenfunktion (z. B. durch Zytokine) in einer Vielzahl der Regulationsprozesse mit involviert ist. So kommt es durch moderat-intensive körperliche Aktivität zu einer Stärkung des Immunsystems mit konsekutiv verminderter Infektanfälligkeit sowie eher anti-inflammatorischen Effekten, wohingegen langandauernde und höher intensive Belastungen zu einer Schwächung der Abwehrfunktion sowie einem pro-inflammatorischen Effekt führen. Somit stellt eine adäquat dosierte körperliche Aktivität eine erfolgversprechende Therapieoption bei Erkrankungen des infektiologischen Formenkreises sowie des Immunsystems dar.

negative: Field Disease Diagnostic Investigation of Neonatal Calf Diarrhea Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life. Field investigations of outbreaks of neonatal calf diarrhea should be conducted for the purposes of (1) reducing the losses associated with existing cases and (2) preventing new cases from occurring. The appropriate corrective actions are determined by taking a population approach to diagnostics and prevention. It can be difficult to provide solutions to disease outbreaks, but success is more likely if an organized, epidemiologic approach to outbreak investigation is followed.

negative: Correlations of Online Search Engine Trends With Coronavirus Disease (COVID-19) Incidence: Infodemiology Study BACKGROUND: The coronavirus disease (COVID-19) is the latest pandemic of the digital age. With the internet harvesting large amounts of data from the general population in real time, public databases such as Google Trends (GT) and the Baidu Index (BI) can be an expedient tool to assist public health efforts. OBJECTIVE: The aim of this study is to apply digital epidemiology to the current COVID-19 pandemic to determine the utility of providing adjunctive epidemiologic information on outbreaks of this disease and evaluate this methodology in the case of future pandemics. METHODS: An epidemiologic time series analysis of online search trends relating to the COVID-19 pandemic was performed from January 9, 2020, to April 6, 2020. BI was used to obtain online search data for China, while GT was used for worldwide data, the countries of Italy and Spain, and the US states of New York and Washington. These data were compared to real-world confirmed cases and deaths of COVID-19. Chronologic patterns were assessed in relation to disease patterns, significant events, and media reports. RESULTS: Worldwide search terms for shortness of breath, anosmia, dysgeusia and ageusia, headache, chest pain, and sneezing had strong correlations (r>0.60, P<.001) to both new daily confirmed cases and deaths from COVID-19. GT COVID-19 (search term) and GT coronavirus (virus) searches predated real-world confirmed cases by 12 days (r=0.85, SD 0.10 and r=0.76, SD 0.09, respectively, P<.001). Searches for symptoms of diarrhea, fever, shortness of breath, cough, nasal obstruction, and rhinorrhea all had a negative lag greater than 1 week compared to new daily cases, while searches for anosmia and dysgeusia peaked worldwide and in China with positive lags of 5 days and 6 weeks, respectively, corresponding with widespread media coverage of these symptoms in COVID-19. CONCLUSIONS: This study demonstrates the utility of digital epidemiology in providing helpful surveillance data of disease outbreaks like COVID-19. Although certain online search trends for this disease were influenced by media coverage, many search terms reflected clinical manifestations of the disease and showed strong correlations with real-world cases and deaths.

negative: Estimating cases of COVID-19 from Daily Death Data in Italy COVID-19 is an emerging infectious disease which has been declared a pan- demic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate. Methods: We present an estimate of the number of cases of COVID-19 com- pared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom on- set to death and reported case fatality rate. Results: Our model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days.

negative: Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy

negative: Predicting the mortality due to Covid-19 by the next month for Italy, Iran and South Korea; A simulation study Aim: To estimate the number of confirmed cases and the rate of death and also to investigate the cause of death in Italy, Iran and South Korea in the next month. Background: Growing number of confirmed and deaths cases from the coronavirus worldwide, particularly in Italy, Iran and South Korea, has resulted concerns about the future of these countries and their deterioration. Also the European region is likely to face more casualties due to the delay in the virus reaching most of its regions and, of course, as the trend continues. Methods: We conducted a simulation in both current and ideal situation for the next month to predict the death rate and examine the reason for the difference in Italy, Iran and South Korea individually. If we assume the cultural and political factors and age pyramids distribution are similar across regions, the differences are mainly due either to the heavier health-care burden owing to the larger population or to the medical facilities diversities. Results: Our results for Italy showed higher death number, but the rate would be more for Iran. South Korea is also expected to have a smaller increase in the number of confirmed cases and deaths compared to Iran and Italy by the next month. Conclusion: Given the prevailing conditions around the world and the increasing number of casualties, it is essential that all countries, especially those with fewer days of involvement, shall do their best to avoid major losses and damages.

negative: The effects of natural disasters on international tourism: A global analysis Tourism is shaped by a wide range of factors and forces, including exogenous ones that have no direct link with the tourism sector. Natural disasters and unexpected events are prime examples of such determining factors, as they have profound effects on individuals and society, and as a result have the potential to affect tourism flows considerably. Several theoretical arguments exist why natural disasters and unexpected events could influence tourist destination choices. However, empirical research to confirm the nature and extent of impacts of disasters on tourism is lacking. To address this gap, this paper incorporates a dataset on natural and man-made disaster events into a model of international tourism flows to evaluate the effect of different types of disasters on international arrivals at the national level. Findings provide evidence that the occurrence of different types of event change tourist flows to varying degrees. Although in some cases a positive effect is estimated, in general the impacts are negative, resulting in reduced tourist arrivals following an event. Understanding the relationship between disaster events and tourism is helpful for destination managers who make critical decisions in relation to recovery, reconstruction and marketing.

negative: Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia Not all persons infected with Middle East respiratory syndrome coronavirus (MERS-CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed.

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: Molecular Screening by Polymerase Chain Reaction Detects Panleukopenia Virus DNA in Formalin-Fixed Hearts from Cats with Idiopathic Cardiomyopathy and Myocarditis Abstract Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.

negative: Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.

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

negative: Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.

negative: COVID-19 (Novel Coronavirus 2019) - recent trends. The World Health Organization (WHO) has issued a warning that, although the 2019 novel coronavirus (COVID-19) from Wuhan City (China), is not pandemic, it should be contained to prevent the global spread. The COVID-19 virus was known earlier as 2019-nCoV. As of 12 February 2020, WHO reported 45,171 cases and 1115 deaths related to COVID-19. COVID-19 is similar to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) virus in its pathogenicity, clinical spectrum, and epidemiology. Comparison of the genome sequences of COVID-19, SARS-CoV, and Middle East Respiratory Syndrome coronavirus (MERS-CoV) showed that COVID-19 has a better sequence identity with SARS-CoV compared to MERS CoV. However, the amino acid sequence of COVID-19 differs from other coronaviruses specifically in the regions of 1ab polyprotein and surface glycoprotein or S-protein. Although several animals have been speculated to be a reservoir for COVID-19, no animal reservoir has been already confirmed. COVID-19 causes COVID-19 disease that has similar symptoms as SARS-CoV. Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV. The nucleocapsid (N) protein of COVID-19 has nearly 90% amino acid sequence identity with SARS-CoV. The N protein antibodies of SARS-CoV may cross react with COVID-19 but may not provide cross-immunity. In a similar fashion to SARS-CoV, the N protein of COVID-19 may play an important role in suppressing the RNA interference (RNAi) to overcome the host defense. This mini-review aims at investigating the most recent trend of COVID-19.

negative: Coronaviren: von der banalen Erkältung zum schweren Lungenversagen: Chronologie einer Pandemie In December 2019 a new human coronavirus emerged in Wuhan, China, which is known as SARS-CoV‑2. The clinical course of the disease known as coronavirus disease 2019 (COVID-19) ranges from mild respiratory symptoms to severe lung failure. The virus is currently rapidly spreading around the world and pushing health systems to the limits of their capacity due to the exponential increase in the number of cases. The origin of SARS-CoV‑2 lies in the bat coronavirus pool and has now emerged in the human population due to interspecies transmission. Molecular diagnostic methods have been established in a very short time and a number of clinical studies on the effectiveness of different antiviral drugs are ongoing. The development of a vaccine using different approaches is also under investigation. Considering the high number of cases and mortality rates of up to 9% there is an urgent need for action. This article summarizes the current state of knowledge on human coronaviruses with a strong focus on the current data on SARS-CoV‑2. Due to the daily changing level of knowledge, the article reflects the status up to 21 March 2020.

negative: Risk Assessment of Novel Coronavirus COVID-19 Outbreaks Outside China We developed a computational tool to assess the risks of novel coronavirus outbreaks outside of China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; and (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number [Formula: see text]). We found that in countries with low connectivity to China but with relatively high [Formula: see text] , the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low [Formula: see text] benefit the most from policies that further reduce [Formula: see text]. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia, and Europe. We investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.

negative: Socioeconomic, geographic and climatic risk factors for canine parvovirus infection and euthanasia in Australia Abstract Infection of canids with canine parvovirus (CPV) can result in severe, often fatal disease. This study aimed to examine climatic, socioeconomic and geographic risk factors for CPV infection and CPV-associated euthanasia in Australia. Australian veterinary hospital responses (534; 23.5 %) to a national veterinary survey of CPV case occurrences and euthanasias in 2016 were used. Severe caseloads (>40 cases per annum) were reported by 26 (11 %) hospitals (median 60 cases; IQR 50–110). Case reporting, case numbers, and without-treatment euthanasia were significantly associated with disadvantage across all Socio-Economic Index for Areas quintiles (p < 0.0001) – the greater the disadvantage, the more reports. Strong negative correlations were found between case numbers and the Index of Relative Socioeconomic Disadvantage (rSP = –0.3357, p < 0.0001) and also between euthanasia and the Index of Education and Occupation (rSP = –0.3762, p < 0.0001). Hospitals in more remote areas were also more likely to report cases and to euthanize without treatment (p < 0.0001). Of the climate variables, temperature of the hottest month was most strongly positively correlated with case numbers (rSP = 0.421, p < 0.0001), and lower annual rainfall was associated with more case-reporting hospitals (p < 0.0001). These results confirm that socioeconomic disadvantage is a significant risk-factor for CPV infection and outcome, and high temperature may also contribute to risk.

negative: Coronavirus threat to Indian population: risk factors, transmission dynamics and preparedness to prevent the spread of the virus Recent novel coronavirus outbreak in Wuhan City of Hubei province in China infected nearly 70,000 individuals and killed more than 1700 people within a short span of time leading to global pandemic. The disease is now spread to 26 countries in Asia, North America, Europe and Australasia. The virus is spreading rapidly to Asia-pacific and Southeast Asian countries. The disease is posing a serious threat to human population and has devastating impact on public health and economy. So far 3 Indians are infected and India is at risk of rapid spread of the disease because of its geographical location and other favorable conditions. With a poorer global health security index compared to China (India-57 and China-51), any such situation will have worse outcome. In near future there are also possibilities of similar kind of disease outbreak caused by new strains of coronaviruses due to factors like species jump of new viruses, high population density and inadequate medical facilities. In this short review we have highlighted the risk factors and transmission dynamics of coronaviruses that may pose a serious threat to India. We have also discussed about the possible preventive measure our country should take to control any such outbreak situation.

negative: Current status and progress of 2019 novel coronavirus pneumonia/ 中华危重病急救医学 Recently, the 2019 novel coronavirus (2019-nCoV) pneumonia outbroke in Wuhan and rapidly spread to all over China and even the world. Because of the strong infectivity and various clinical symptoms, it has brought certain difficulties to the epidemic prevention and control. Currently there is no specific drug for 2019-nCoV. Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed. We reviewed literature on the epidemiology, etiology, clinical manifestations, imaging manifestations, laboratory examination, diagnosis, complications, treatment and outcome of 2019-nCoV pneumonia.

negative: A Model for the Testing and Tracing Needed to Suppress COVID-19 This paper presents a simple mathematical model that answers how much testing and tracing we need to do to suppress new surges of COVID-19 infections after reopening. We derived the model by modifying the SEIR model taking into the effects of testing and tracing. The following equation is one of the essential outcomes of the model: {rho}>(R0S/N-1)/(D(1+{eta}R0)) Where {rho} is the percentage of infectious people that have to be detected per day, R0 is the basic reproduction number, S/N is the percentage of the susceptible population over the entire population, D is the length of the infectious period, and {eta} is the percentage of close contacts that have to be traced. If the above equation is satisfied, we can bring the effective reproduction number Re to below 1 to get the transmission suppressed. This model demonstrates that together with social-distancing measures such as wearing masks in public, with a reasonable amount of testing and tracing, we may suppress the COVID-19 transmission for good. For example, if social distancing measures can bring R0 to below 1.2, for D being 10 days, in places where 15% people have developed antibodies, we can suppress the transmission by detecting only 0.13% of the infectious population daily while tracing 50% of their close contacts. The model provides intuitive insights and quantitative guidance for policymakers and public health practitioners to deploy the testing and tracing resources optimally.

negative: "Go eat a bat, Chang!": An Early Look on the Emergence of Sinophobic Behavior on Web Communities in the Face of COVID-19 The outbreak of the COVID-19 pandemic has changed our lives in unprecedented ways. In the face of the projected catastrophic consequences, many countries have enacted social distancing measures in an attempt to limit the spread of the virus. Under these conditions, the Web has become an indispensable medium for information acquisition, communication, and entertainment. At the same time, unfortunately, the Web is being exploited for the dissemination of potentially harmful and disturbing content, such as the spread of conspiracy theories and hateful speech towards specific ethnic groups, in particular towards Chinese people since COVID-19 is believed to have originated from China. In this paper, we make a first attempt to study the emergence of Sinophobic behavior on the Web during the outbreak of the COVID-19 pandemic. We collect two large-scale datasets from Twitter and 4chan's Politically Incorrect board (/pol/) over a time period of approximately five months and analyze them to investigate whether there is a rise or important differences with regard to the dissemination of Sinophobic content. We find that COVID-19 indeed drives the rise of Sinophobia on the Web and that the dissemination of Sinophobic content is a cross-platform phenomenon: it exists on fringe Web communities like \dspol, and to a lesser extent on mainstream ones like Twitter. Also, using word embeddings over time, we characterize the evolution and emergence of new Sinophobic slurs on both Twitter and /pol/. Finally, we find interesting differences in the context in which words related to Chinese people are used on the Web before and after the COVID-19 outbreak: on Twitter we observe a shift towards blaming China for the situation, while on /pol/ we find a shift towards using more (and new) Sinophobic slurs.

negative: NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Trypanosoma cruzi Acute Infection Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T. cruzi-Tulahuen strain acute infection. We demonstrated that infected nlrp3−/− and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of nlrp3−/− mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and nlrp3−/− mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, caspase-1/11−/− mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, caspase-1/11−/− mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation.

negative: Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease SARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 μM and 0.04 μM respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 μM and 0.33 μM, respectively. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a and 11b were determined at 1.5 Å resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.

negative: SARS Transmission, Risk Factors, and Prevention in Hong Kong We analyzed information obtained from 1,192 patients with probable severe acute respiratory syndrome (SARS) reported in Hong Kong. Among them, 26.6% were hospital workers, 16.1% were household members of SARS patients and had probable secondary infections, 14.3% were Amoy Garden residents, 4.9% were inpatients, and 20.1% were contacts of SARS patients who were not family members. The remaining 347 case-patients (29.1%) did not have “known” sources of infection. Excluding those <16 years of age, 330 patients with cases from “undefined” sources were used in a 1:2 matched case-control study. Multivariate analysis of this case-control study showed that having visited mainland China, hospitals, or the Amoy Gardens were risk factors (odds ratio [OR] 1.95 to 7.63). In addition, frequent mask use in public venues, frequent hand washing, and disinfecting the living quarters were significant protective factors (OR 0.36 to 0.58). In Hong Kong, therefore, community-acquired infection did not make up most transmissions, and public health measures have contributed substantially to the control of the SARS epidemic.

negative: Outbreak analysis with a logistic growth model shows COVID-19 suppression dynamics in China China experienced an outbreak of a novel coronavirus, SARS-CoV2, from mid-January till mid-March 2020. Here we review the curves of epidemic growth and decline of the virus in China using a phenomenological logistic growth model to summarize the dynamics of the outbreak using three parameters that characterize the epidemic's timing, rate and peak. During the initial phase, the number of cases doubled every 2.7 (range 2.2 - 4.4) days. The rate of increase in the number of reported cases peaked approximately 10 days after suppression measures were started on 23-25 January 2020. The peak in the number of reported sick cases occurred on average 18 days after the start of measures. From the time of starting measures till the peak, the number of cases increased by a factor 38.5 in the province Hubei, and by a factor 9.5 for all of China (range: 6.2-20.4 in the other provinces). Complete suppression took up to 2 months (range: 23-57d.), during which period severe restrictions, social distancing measures, testing and isolation of cases were in place. The suppression of the disease in China has been successful, acting as a beacon of hope for countries outside China where the epidemic is still in a phase of increase and authorities need to decide their course of action.

negative: Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Last decade witnessed the outbreak of many life-threatening human pathogens including Nipah, Ebola, Chikungunya, Zika, Middle East respiratory syndrome coronavirus (MERS-CoV), Severe Acute respiratory syndrome coronavirus (SARS-CoV) and more recently novel coronavirus (2019-nCoV or SARS-CoV-2). The disease condition associated with novel coronavirus, referred to as Coronavirus disease (COVID-19). The emergence of novel coronavirus in 2019 in Wuhan, China marked the third highly pathogenic coronavirus infecting humans in the 21st century. The continuing emergence of coronaviruses at regular intervals poses a significant threat to human health and economy. Ironically, even after a decade of research on coronavirus, still there are no licensed vaccines or therapeutic agents to treat coronavirus infection which highlights an urgent need to develop effective vaccines or post-exposure prophylaxis to prevent future epidemics. Several clinical, genetic and epidemiological features of COVID-19 resemble SARS-CoV infection. Hence, the research advancements on SARS-CoV treatment might help scientific community in quick understanding of this virus pathogenesis and develop effective therapeutic/prophylactic agents to treat and prevent this infection. Monoclonal antibodies represent the major class of biotherapeutics for passive immunotherapy to fight against viral infection. The therapeutic potential of monoclonal antibodies has been well recognized in the treatment of many diseases. Here, we summarize the potential monoclonal antibody based therapeutic intervention for COVID-19 by considering the existing knowledge on the neutralizing monoclonal antibodies against similar coronaviruses SARS-CoV and MERS-CoV. Further research on COVID-19 pathogenesis could identify appropriate therapeutic targets to develop specific anti-virals against this newly emerging pathogen.

negative: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent's country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.

negative: Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19 Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

negative: Chapter 13 National Health Systems Abstract Health care systems ideally include universal access to comprehensive prepaid medical care along with health promotion and disease prevention. National health insurance and national health services of various models have evolved in the developed world and increasingly in developing countries as well. Some models, such as the Bismarckian social security model and the Bereidge National Health Service model, or National Health insurance such as in pioneered in Canada, are used by a number of countries. The common features are based on principles of national responsibility and solidarity for health, social solidarity for providing funding and searching for effective ways of providing care. Various universal systems of health coverage exist in all industrialized countries, except in the United States which has a mix of public and private insurance but with high percentages of uninsured and poorly insured. Health reform is a continuing process as all countries aspire to assure health care for all. Aging populations, increasing costs, advancing and increasing technology all require nations to modify and adapt organization and financing systems of health care, health protection and promotion.

negative: Feasibility of Controlling COVID-19 Outbreaks in the UK by Rolling Interventions Background: Recent outbreak of a novel coronavirus disease 2019 (COVID-19) in China has led a rapid global spread around the world. For controlling COVID-19 outbreaks, many countries have implemented two non-pharmaceutical interventions: suppression like immediate lockdowns in cities at epicentre of outbreak; or mitigation that slows down but not stopping epidemic for reducing peak healthcare demand. Both interventions have apparent pros and cons; the effectiveness of any one intervention in isolation is limited. We aimed to conduct a feasibility study for robustly estimating the number and distribution of infections, growth of deaths, peaks and lengths of COVID-19 breakouts by taking multiple pharmaceutical interventions in London and the UK, accounting for reduction of healthcare demand. Methods: We developed a model to attempt to infer the impact of mitigation, suppression and multiple rolling interventions for controlling COVID-19 outbreaks in London and the UK. Our model assumed that each intervention has equivalent effect on the reproduction number R across countries and over time; where its intensity was presented by average-number contacts with susceptible individuals as infectious individuals; early immediate intensive intervention led to increased health need and social anxiety. We considered two important features: direct link between Exposed and Recovered population, and practical healthcare demand by separation of infections into mild and critical cases. Our model was fitted and calibrated with data on cases of COVID-19 in Wuhan and Hubei to estimate how suppression intervention impacted on the number and distribution of infections, growth of deaths over time during January 2020, and April 2020. We combined the calibrated model with data on the cases of COVID-19 in London, the UK (non-London) and the UK during February 2020 and March 2020 to estimate the number and distribution of infections, growth of deaths, and healthcare demand by using multiple interventions. Findings: We estimated given that multiple interventions with an intensity range from 3 to 15, one optimal strategy was to take suppression with intensity 3 in London from 23rd March for 100 days, and 3 weeks rolling intervention with intensity between 3 and 5 in non-London regions. In this scenario, the total infections and deaths in the UK were limited to 2.43 million and 33.8 thousand; the peak time of healthcare demand was due to the 65th day (April 11th), where it needs hospital beds for 25.3 thousand severe and critical cases. If we took a simultaneous 3 weeks rolling intervention with intensity between 3 and 5 in all regions of the UK, the total infections and deaths increased slightly to 2.69 million and 37 thousand; the peak time of healthcare kept the same at the 65th day, where it needs equivalent hospital beds for severe and critical cases of 25.3 thousand. But if we released high band of rolling intervention intensity to 6 or 8 and simultaneously implemented them in all regions of the UK, the COVID-19 outbreak would not end in 1 year and distribute a multi-modal mode, where the total infections and deaths in the UK possibly reached to 16.2 million and 257 thousand.

negative: The computation of case fatality rate for novel coronavirus (COVID-19) based on Bayes theorem: An observational study BACKGROUND: When a new disease such starts to spread, the commonly asked questions are how deadly is it? and how many people are likely to die of this outbreak? The World Health Organization (WHO) announced in a press conference on January 29, 2020 that the death rate of COVID-19 was 2% on the case fatality rate (CFR). It was underestimated assuming no lag days from symptom onset to deaths while many CFR formulas have been proposed, the estimation on Bays theorem is worthy of interpretation. Hence, it is hypothesized that the over-loaded burdens of treating patients and capacities to contain the outbreak (LSBHRS) may increase the CFR. METHODS: We downloaded COVID-19 outbreak numbers from January 21 to February 14, 2020, in countries/regions on a daily basis from Github that contains information on confirmed cases in >30 Chinese locations and other countries/regions. The pros and cons were compared among the 5 formula of CFR, including [A] deaths/confirmed; [B] deaths/(deaths + recovered); [C] deaths/(cases x days ago); [D] Bayes estimation based on [A] and the outbreak (LSBHRS) in each country/region; and [E] Bayes estimation based on [C] deaths/(cases x days ago). The coefficients of variance (CV = the ratio of the standard deviation to the mean) were applied to measure the relative variability for each CFR. A dashboard was developed for daily display of the CFR across each region. RESULTS: The Bayes based on (A)[D] has the lowest CV (=0.10) followed by the deaths/confirmed (=0.11) [A], deaths/(deaths + recoveries) (=0.42) [B], Bayes based on (C) (=0.49) [E], and deaths/(cases x days ago) (=0.59) [C]. All final CFRs will be equal using the formula (from, A to E). A dashboard was developed for the daily reporting of the CFR. The CFR (3.7%) greater than the prior CFR of 2.2% was evident in LSBHRS, increasing the CFR. A dashboard was created to present the CFRs on COVID-19. CONCLUSION: We suggest examining both trends of the Bayes based on both deaths/(cases 7 days ago) and deaths/confirmed cases as a reference to the final CFR. An app developed for displaying the provisional CFR with the 2 CFR trends can improve the underestimated CFR reported by WHO and media.

negative: Dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a Coronavirus Disease 2019 patient Abstract We report the dynamic change process of target genes by RT-PCR testing of SARS-Cov-2 during the course of a COVID-19 patient: from successive negative results to successive single positive nucleocapsid gene, to two positive target genes (orf1ab and nucleocapsid) by RT-PCR testing of SARS-Cov-2, and describe the diagnosis, clinical course, and management of the case. In this case, negative results of RT-PCR testing was not excluded to diagnose a suspected COVID-19 patient, clinical signs and symptoms, other laboratory findings, and chest CT images should be taken into account for the absence of enough positive evidence. This case highlights the importance of successive sampling and testing SARS-Cov-2 by RT-PCR as well as the increased value of single positive target gene from pending to positive in two specimens to diagnose laboratory-confirmed COVID-19.

negative: Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a cAMP-regulated anion channel. Although CF is a multi-organ system disease, most people with CF die of progressive lung disease that begins early in childhood and is characterized by chronic bacterial infection and inflammation. Nearly 90% of people with CF have at least one copy of the ΔF508 mutation, but there are hundreds of CFTR mutations that result in a range of disease severities. A CFTR gene replacement approach would be efficacious regardless of the disease-causing mutation. After the discovery of the CFTR gene in 1989, the in vitro proof-of-concept for gene therapy for CF was quickly established in 1990. In 1993, the first of many gene therapy clinical trials attempted to rescue the CF defect in airway epithelia. Despite the initial enthusiasm, there is still no FDA-approved gene therapy for CF. Here we discuss the history of CF gene therapy, from the discovery of the CFTR gene to current state-of-the-art gene delivery vector designs. While implementation of CF gene therapy has proven more challenging than initially envisioned; thanks to continued innovation, it may yet become a reality.

negative: What Should Gastroenterologists and Patients Know About COVID-19?

negative: Tracking the reach of COVID-19 kin loss with a bereavement multiplier applied to the United States. The coronavirus disease 2019 (COVID-19) pandemic has led to a large increase in mortality in the United States and around the world, leaving many grieving the sudden loss of family members. We created an indicator-the COVID-19 bereavement multiplier-that estimates the average number of individuals who will experience the death of a close relative (defined as a grandparent, parent, sibling, spouse, or child) for each COVID-19 death. Using demographic microsimulation-based estimates of kinship networks in the United States, the clear age gradient in COVID-19 mortality seen across contexts, and several hypothetical infection prevalence scenarios, we estimate COVID-19 bereavement multipliers for White and Black individuals in the United States. Our analysis shows that for every COVID-19 death, approximately nine surviving Americans will lose a grandparent, parent, sibling, spouse, or child. These estimates imply, for example, that if 190,000 Americans die from COVID-19, as some models project, then ∼1.7 million will experience the death of a close relative. We demonstrate that our estimates of the bereavement multiplier are stable across epidemiological realities, including infection scenarios, total number of deaths, and the distribution of deaths, which means researchers can estimate the bereavement burden over the course of the epidemic in lockstep with rising death tolls. In addition, we provide estimates of bereavement multipliers by age group, types of kin loss, and race to illuminate prospective disparities. The bereavement multiplier is a useful indicator for tracking COVID-19's multiplicative impact as it reverberates across American families and can be tailored to other causes of death.

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: Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated.

negative: Tracking COVID-19 by Tracking Infectious Trajectories Nowadays, the coronavirus pandemic has and is still causing large numbers of deaths and infected people. Although governments all over the world have taken severe measurements to slow down the virus spreading (e.g., travel restrictions, suspending all sportive, social, and economic activities, quarantines, social distancing, etc.), a lot of persons have died and a lot more are still in danger. Indeed, a recently conducted study~\cite{ref2} has reported that 79\% of the confirmed infections in China were caused by undocumented patients who had no symptoms. In the same context, in numerous other countries, since coronavirus takes several days before the emergence of symptoms, it has also been reported that the known number of infections is not representative of the real number of infected people (the actual number is expected to be much higher). That is to say, asymptomatic patients are the main factor behind the large quick spreading of coronavirus and are also the major reason that caused governments to lose control over this critical situation. To contribute to remedying this global pandemic, in this paper, we propose an IoT (Internet of Things) investigation system that was specifically designed to spot both undocumented patients and infectious places. The goal is to help the authorities to disinfect high-contamination sites and confine persons even if they have no apparent symptoms. The proposed system also allows determining all persons who had close contact with infected or suspected patients. Consequently, rapid isolation of suspicious cases and more efficient control over any pandemic propagation can be achieved.

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: Moving-average based index to timely evaluate the current epidemic situation after COVID-19 outbreak A pneumonia outbreak caused by a novel coronavirus (COVID-19) occurred in Wuhan, China at the end of 2019 and then spread rapidly to the whole country. A total of 81,021 laboratory-confirmed cases, including 3,194 deaths (3.9%) had been reported in China by March 14, 2020, meanwhile, 61,518 laboratory-confirmed cases and 2,199 deaths were reported outside China. Common symptoms of COVID-19 pneumonia included fever, fatigue and dry cough. Faced with such a sudden outbreak of new infectious diseases, we have no history to learn from and no evidence to count on. Traditional models often predict inconsistent results. Aiming at estimate the epidemic trend timely after the outbreak, we mainly used 7-day moving average of log-transformed daily new cases (LMA) to establish a new index named "epidemic trend index", which will be used to predict the evolutionary trend of the epidemic situation and support epidemic control decision making processes. We used SARS epidemic data from Hong Kong in 2003 to verify the practicability of the new index, which shows that the index is acceptable. The epidemic trend index was then applied to the COVID-19 epidemic analysis in China. The results show that during the epidemic, the trend direction of different districts of China changed on different date. In the whole country and in Hubei Province alone, the epidemic reached the peak on February 9. While the peak appeared earlier, i.e. on February 5 in other provinces. It indicated that decisive outbreak control measures of the Chinese government are effective. While local governments should adjust management measures based on local risk level of epidemic. Although the epidemic has eased since late February, continued efforts in epidemic control are still needed to accelerate the end of the epidemic in China. However, the global COVID-19 epidemic outside China continues to expand as indicated by the epidemic trend index we proposed. In order to cope with the novel coronavirus pandemic, people all over the world should work together and governments of all countries should take efficient measures in the light of China's experience and according to national circumstances and local conditions.

negative: Commentary: When a cardiac surgeon takes care of patients with Coronavirus Disease 2019: It’s gonna be ok!

negative: What can trends in hospital deaths from COVID-19 tell us about the progress and peak of the pandemic? An analysis of death counts from England announced up to 25 April 2020 Background. Reporting of daily hospital COVID-19 deaths in the UK are promoted by the government and scientific advisers alike as a key metric for assessing the progress in the control of the epidemic. These data, however, have certain limitations, among which one of the most significant concerns the fact that the daily totals span deaths that have occurred between 1 and 10 days or more in the past. Data and methods. We obtained daily data published published by NHS England up to and including April 25 in the form of Excel spreadsheets in which deaths counts are presented by date of death according to age and region. Simple descriptive analyses were conducted and presented in graphical and tabular form which were aimed at illustrating the biases inherent in focussing on daily counts regardless of when the deaths occurred. We then looked at how a less biased picture could be obtained by looking at trends in death counts stratifying by individual period of delay in days between occurrence of death and when the death was included in the daily announcement. Findings. The number of hospital COVID-19 deaths announced daily overestimates the maximum number of deaths actually occurring so far in the epidemic in the UK, and also obscures the pattern of decline in deaths. Taking account of reporting delays suggests that for England as a whole a peak in hospital COVID-19 deaths may have been reached on April 8 with a subsequent gradual decline suggested. The same peak is also seen among those aged 60-79 and 80+, although there is slightly shallower decline in the oldest age group (80+ years). Among those aged 40-59 years a later peak on April 11 is evident. London shows a peak on April 8 and a clearer and steeper pattern of subsequent decline compared to England as a whole. Interpretation. Analyses of mortality trends must take account of delay, and in communication with the public more emphasis should be placed on looking at trends based on deaths that occurred 5 or more days prior to the announcement day. The slightly weaker decline seen at age 80+ may reflect increased hospitalisation of people from care homes, whereas the later peak under the age of 60 years may reflect the higher proportions at these younger ages being admitted to critical care resulting in an extension of life of several days.

negative: Dynamic causal modelling of COVID-19 This technical report describes a dynamic causal model of the spread of coronavirus through a population. The model is based upon ensemble or population dynamics that generate outcomes, like new cases and deaths over time. The purpose of this model is to quantify the uncertainty that attends predictions of relevant outcomes. By assuming suitable conditional dependencies, one can model the effects of interventions (e.g., social distancing) and differences among populations (e.g., herd immunity) to predict what might happen in different circumstances. Technically, this model leverages state-of-the-art variational (Bayesian) model inversion and comparison procedures, originally developed to characterise the responses of neuronal ensembles to perturbations. Here, this modelling is applied to epidemiological populations to illustrate the kind of inferences that are supported and how the model per se can be optimised given timeseries data. Although the purpose of this paper is to describe a modelling protocol, the results illustrate some interesting perspectives on the current pandemic; for example, the nonlinear effects of herd immunity that speak to a self-organised mitigation process.

negative: Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2 The recent outbreak of a new coronavirus (SARS-CoV-2) in Wuhan, China, underscores the need for understanding the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. Here, we show that recombination in betacoronaviruses, including human-infecting viruses like SARS-CoV and MERS-CoV, frequently encompasses the Receptor Binding Domain (RBD) in the Spike gene. We find that this common process likely led to a recombination event at least 11 years ago in an ancestor of the SARS-CoV-2 involving the RBD. As a result of this recombination event, SARS-CoV and SARS-CoV-2 share a similar genotype in RBD, including two insertions (positions 432-436 and 460-472), and alleles 427N and 436Y. Both 427N and 436Y belong to a helix that interacts with the human ACE2 receptor. Ancestral state analyses revealed that SARS-CoV-2 differentiated from its most recent common ancestor with RaTG13 by accumulating a significant number of amino acid changes in the RBD. In sum, we propose a two-hit scenario in the emergence of the SARS-CoV-2 virus whereby the SARS-CoV-2 ancestors in bats first acquired genetic characteristics of SARS-CoV by incorporation of a SARS-like RBD through recombination before 2009, and subsequently, the lineage that led to SARS-CoV-2 accumulated further, unique changes specifically in the RBD.

negative: Chapter 12 Early Warning Practice Using Internet-Based Data Abstract On the Internet, there is a lot of open access information related to infectious diseases, e.g., official announcement, media news, bulletin boards, blogs, and other social media. If proper data retrieval and screening methods were applied on these Internet-based data, it would be very useful to improve the timeliness of early detection for infectious diseases. In China, we practice early warning using Internet-based data with routine intelligence screening assessment every day, and respond to any unusual event in a timely manner. Through this mechanism, the surveillance and early warning of Internet-based data for infectious disease and public health emergency plays an important supplemental role to the traditional surveillance systems.

negative: A systematic review and meta-analysis of published research data on COVID-19 infection-fatality rates Introduction: An important unknown during the COVID-19 pandemic has been the infection-fatality rate (IFR). This differs from the case-fatality rate (CFR) as an estimate of the number of deaths as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy-makers and the lay public as an estimate of the overall mortality from COVID-19. Methods: Pubmed and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. Results: After exclusions, there were 13 estimates of IFR included in the final meta-analysis, from a wide range of countries, published between February and April 2020. The meta-analysis demonstrated a point-estimate of IFR of 0.75% (0.49-1.01%) with significant heterogeneity (p<0.001). Conclusion: Based on a systematic review and meta-analysis of published evidence on COVID-19 until the end of April, 2020, the IFR of the disease across populations is 0.75% (0.49-1.01%). However, due to very high heterogeneity in the meta-analysis, it is difficult to know if this represents the "true" point estimate. It is likely that different places will experience different IFRs. More research looking at age-stratified IFR is urgently needed to inform policy-making on this front.

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: Who goes to a library for cancer information in the e-health era? A secondary data analysis of the Health Information National Trends Survey (HINTS) Abstract This study identifies characteristics of Americans who chose the library as their primary cancer information source over the Internet by examining demographic characteristics, online use experience, concerns of information quality, and perceptions of cancer information seeking. A secondary data analysis is conducted using the Health Information National Trends Survey (HINTS) of the National Cancer Institute (NCI). Findings reveal that people who are more likely to choose the library are, compared to their Internet counterparts, people who lack online experience, are distrustful of online cancer information, and are more aware of cancer sources. However, they are not necessarily more adept cancer information seekers and do not have a greater expectation of getting quality information from the library. These findings suggest how the library plays its role as an information source for cancer information consumers in the e-health environment. Implications of the findings are discussed in a way that libraries could invest their efforts to reduce the digital health divide and to advance consumer health information literacy.

negative: Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics.

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: 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: Chapter 15 Biology and Diseases of Ruminants (Sheep, Goats, and Cattle) Ruminants continue to be important in their traditional role in agricultural research and teaching. They are now also extensively used for studies in molecular biology; genetic engineering; and biotechnology for basic science, agricultural and clinical applications. Concern and interest for the welfare for these species and improved understanding of their biology and behavior have continued and are reflected in changing husbandry and management systems. This chapter addresses at high levels basic biology, husbandry, and the more common or important diseases of the three ruminant species used most commonly in the laboratory, namely sheep, goats and cattle.

negative: Modelling death rates due to COVID-19: A Bayesian approach Objective: To estimate the number of deaths in Peru due to COVID-19. Design: With a priori information obtained from the daily number of deaths due to CODIV-19 in China and data from the Peruvian authorities, we constructed a predictive Bayesian non-linear model for the number of deaths in Peru. Exposure: COVID-19. Outcome: Number of deaths. Results: Assuming an intervention level similar to the one implemented in China, the total number of deaths in Peru is expected to be 612 (95%CI: 604.3 - 833.7) persons. Sixty four days after the first reported death, the 99% of expected deaths will be observed. The inflexion point in the number of deaths is estimated to be around day 26 (95%CI: 25.1 - 26.8) after the first reported death. Conclusion: These estimates can help authorities to monitor the epidemic and implement strategies in order to manage the COVID-19 pandemic.

negative: Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis. Background An ongoing outbreak of pneumonia caused by a novel coronavirus [severe acute respiratory syndrome coronavirus (SARS-CoV)-2], named COVID-19, hit a major city of China, Wuhan in December 2019 and subsequently spread to other provinces/regions of China and overseas. Several studies have been done to estimate the basic reproduction number in the early phase of this outbreak, yet there are no reliable estimates of case fatality rate (CFR) for COVID-19 to date. Methods In this study, we used a purely data-driven statistical method to estimate the CFR in the early phase of the COVID-19 outbreak. Daily numbers of laboratory-confirmed COVID-19 cases and deaths were collected from January 10 to February 3, 2020 and divided into three clusters: Wuhan city, other cities of Hubei province, and other provinces of mainland China. Simple linear regression model was applied to estimate the CFR from each cluster. Results We estimated that CFR during the first weeks of the epidemic ranges from 0.15% (95% CI: 0.12-0.18%) in mainland China excluding Hubei through 1.41% (95% CI: 1.38-1.45%) in Hubei province excluding the city of Wuhan to 5.25% (95% CI: 4.98-5.51%) in Wuhan. Conclusions Our early estimates suggest that the CFR of COVID-19 is lower than the previous coronavirus epidemics caused by SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

negative: Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES: We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene–induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS: These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a “compensation” for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937

negative: The Indian perspective of COVID-19 outbreak The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918–1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.

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: The American College of Nuclear Medicine Guidance on Operating Procedures for a Nuclear Medicine Facility During COVID-19 Pandemic The novel coronavirus 2 pandemic is causing widespread disruption in everyday life necessitating urgent and radical adaptations in operating procedures at Nuclear Medicine facilities. The potential for causing severe illness, COVID-19, calls for strict observance of preventive measures aimed to mitigate the spread of the virus. The threat of COVID-19 is particularly serious as there is no vaccine and no specific antiviral therapy. Further complications are introduced by shortages of personal protective equipment for healthcare workers who have direct contact with patients and effective testing to identify infected patients, raising the need for delaying some testing and therapies. Certain vulnerable segments of the general population have been identified (advanced age and certain comorbidities), which should heighten further their preventive efforts. Therefore, this guidance is intended to be operationalized depending on a facility’s specific needs and local disease prevalence.

negative: Responding to Covid-19: How to Navigate a Public Health Emergency Legally and Ethically Few novel or emerging infectious diseases have posed such vital ethical challenges so quickly and dramatically as the novel coronavirus SARS-CoV-2. The World Health Organization declared a public health emergency of international concern and recently classified Covid-19 as a worldwide pandemic. As of this writing, the epidemic has not yet peaked in the United States, but community transmission is widespread. President Trump declared a national emergency as fifty governors declared state emergencies. In the coming weeks, hospitals will become overrun, stretched to their capacities. When the health system becomes stretched beyond capacity, how can we ethically allocate scarce health goods and services? How can we ensure that marginalized populations can access the care they need? What ethical duties do we owe to vulnerable people separated from their families and communities? And how do we ethically and legally balance public health with civil liberties?

negative: On a Comprehensive Model of the Novel Coronavirus (COVID-19) Under Mittag-Leffler Derivative Abstract The major purpose of the presented study is to analyze and find the solution for the model of nonlinear fractional differential equations (FDEs) describing the deadly and most parlous virus so-called coronavirus (COVID-19). The mathematical model depending of fourteen nonlinear FDEs is presented and the corresponding numerical results are studied by applying the fractional Adams Bashforth (AB) method. Moreover, a recently introduced fractional nonlocal operator known as Atangana-Baleanu (AB) is applied in order to realize more effectively. For the current results, the fixed point theorems of Krasnoselskii and Banach are hired to present the existence, uniqueness as well as stability of the model. For numerical simulations, the behavior of the approximate solution is presented in terms of graphs through various fractional orders. Finally, a brief discussion on conclusion about the simulation is given to describe how the transmission dynamics of infection take place in society.

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: A prototype for decision support tool to help decision-makers with the strategy of handling the COVID-19 UK epidemic The primary objective of this work is to model and compare different exit scenarios from the lock-down for the COVID-19 UK epidemic. In doing so we provide an additional modelling basis for laying out the strategy options for the decision-makers. The main results are illustrated and discussed in Part I. In Part II, we describe the stochastic model that we have developed for modelling this epidemic. As argued in Part II, the developed model is more flexible than the SEIR/SEIRS models and can be used for modelling the scenarios which may be difficult or impossible to model with the SEIR/SEIRS models. To compare different scenarios for exiting from the lock-down, in Part III we provide our previous report on the same topic where similar (although not as detailed) scenarios were considered. As the possible exit dates, we have chosen May 4, May 11, May 18 and May 25. We model differently the regions with high initial reproductive number chosen to be R0=2.5, medium R0=2.3 and low R0=2.The numbers for the whole of the UK can be obtained by appropriate averaging of the numbers given in the report. Typical figures are given in Section 4. For each scenario considered, we plot the expected proportion of infected at time t and the expected number of deaths at time t. To compute the expected numbers of deaths we used the total mortality rate 0.66%. Many recent studies suggest lower values and therefore the numbers in our projections should be considered as rather pessimistic. Our analysis suggests a value around 0.5% for the mortality rate. In the model, we assume that the isolation of older and vulnerable people continues and the public carries on certain level of isolation until the end of 2020; also we assume that immunity is kept for at least a year and there is no international travel influence. Our main conclusions are: In regions with higher initial reproductive number 2.5 the proportion of susceptible at the start of the lock-down should be not smaller than 0.95, the epidemic curve in such regions is in the fast monotonic decline irrespectively of the date of the lock-down lift; In regions with lower initial reproductive number 2.0 the second mild wave can be expected, the difference between the expected mortality rates is very small for all May 2020 lifting lock-down dates; In regions with initial reproductive number 2.3, a mild second wave can be expected in the case of large proportion of susceptible at the start of the lock-down, but its severity and resulting mortality depend very little on the date of lifting the lock-down; For the overall UK epidemic, even for rather pessimistic scenarios considered, the second wave is much less pronounced (in terms of the expected mortality rate) than the first one, and the total numbers of expected deaths are within 2% for all May 2020 dates of lifting the lock-down. Moreover, by keeping R0-value after lifting the lock-down below 1.75 is likely to lead to the avoidance of a UK-wide second wave, see Section 4. We believe that the model build in this work can be considered as an important decision support tool to help decision-makers with the strategy of handling the epidemic. We invite other scholars to participate in an open discussion of the strategy options. We feel that this kind of models should be used in the short and long term management of the disease. We recommend the development of a permanent and modularised modelling suite for COVID-19 management to which additional modules can be added as anti-viral drugs and vaccination are introduced, extending the options. We trust that this work makes a start in that direction and demonstrates the advantages of a heterogeneous demographic refinement, which can only improve targeting role out of treatments.

negative: Hopelessness, helplessness and resilience: The importance of safeguarding our trainees' mental wellbeing during the COVID-19 pandemic • The COVID-19 pandemic may put the mental wellbeing of trainees at risk. • Hopelessness, helplessness and burnout are important to be aware of. • We need to foster an open culture of trust and support. • We need to promote resilience in colleagues/trainees where possible.

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: Singapore's experience of SARS. The coronavirus that causes severe acute respiratory syndrome (SARS) is transmitted mainly via respiratory droplets. Typical presenting symptoms are akin to those of ordinary pneumonia. Young patients start with fever, chills, malaise, headache, or myalgia; cough and dyspnoea follow. Older persons and those taking corticosteroids may have neither fever nor respiratory symptoms. Exceptional suspicion is needed to identify SARS early in the illness. During an outbreak, even patients with low suspicion of SARS should be promptly isolated, and all contacts quarantined. Health workers need training in the use of appropriate barriers against droplets and other body fluids. Any fever cluster in patients or carers requires immediate action: discharges, visits, and transfers between wards and hospitals should be stopped. Halting hospital admissions and ten-day quarantine of suspected cases create wide buffer zones. To counter a possible resurgence of SARS, a system of prepared isolation and quarantine facilities is important.

negative: Putting resiliency of a health system to the test: COVID-19 in Taiwan

negative: Telehealth in the Context of COVID-19: Changing Perspectives in Australia, the United Kingdom, and the United States BACKGROUND: On March 12, 2020, the World Health Organization declared the coronavirus disease (COVID-19) outbreak a pandemic. On that date, there were 134,576 reported cases and 4981 deaths worldwide. By March 26, 2020, just 2 weeks later, reported cases had increased four-fold to 531,865, and deaths increased five-fold to 24,073. Older people are both major users of telehealth services and are more likely to die as a result of COVID-19. OBJECTIVE: This paper examines the extent that Australia, the United Kingdom, and the United States, during the 2 weeks following the pandemic announcement, sought to promote telehealth as a tool that could help identify COVID-19 among older people who may live alone, be frail, or be self-isolating, and give support to or facilitate the treatment of people who are or may be infected. METHODS: This paper reports, for the 2-week period previously mentioned and immediately prior, on activities and initiatives in the three countries taken by governments or their agencies (at national or state levels) together with publications or guidance issued by professional, trade, and charitable bodies. Different sources of information are drawn upon that point to the perceived likely benefits of telehealth in fighting the pandemic. It is not the purpose of this paper to draw together or analyze information that reflects growing knowledge about COVID-19, except where telehealth is seen as a component. RESULTS: The picture that emerges for the three countries, based on the sources identified, shows a number of differences. These differences center on the nature of their health services, the extent of attention given to older people (and the circumstances that can relate to them), the different geographies (notably concerned with rurality), and the changes to funding frameworks that could impact these. Common to all three countries is the value attributed to maintaining quality safeguards in the wider context of their health services but where such services are noted as sometimes having precluded significant telehealth use. CONCLUSIONS: The COVID-19 pandemic is forcing changes and may help to establish telehealth more firmly in its aftermath. Some of the changes may not be long-lasting. However, the momentum is such that telehealth will almost certainly find a stronger place within health service frameworks for each of the three countries and is likely to have increased acceptance among both patients and health care providers.

negative: Patterns of Readmissions for Three Common Conditions Among Younger US Adults Abstract Background Thirty-day readmissions among elderly Medicare patients are an important hospital quality measure. Although plans for using 30-day readmission measures are under consideration for younger patients, little is known about readmission in younger patients or the relationship between readmissions in younger and elderly patients at the same hospital. Methods By using the 2014 Nationwide Readmissions Database, we examined readmission patterns in younger patients (18-64 years) using hierarchical models to evaluate associations between hospital 30-day, risk-standardized readmission rates in elderly Medicare patients and readmission risk in younger patients with acute myocardial infarction, heart failure, or pneumonia. Results There were 87,818, 98,315, and 103,251 admissions in younger patients for acute myocardial infarction, heart failure, and pneumonia, respectively, with overall 30-day unplanned readmission rates of 8.5%, 21.4%, and 13.7%, respectively. Readmission risk in younger patients was significantly associated with hospital 30-day risk-standardized readmission rates for elderly Medicare patients for all 3 conditions. A decrease in an average hospital's 30-day, risk-standardized readmission rates from the 75th percentile to the 25th percentile was associated with reduction in younger patients' risk of readmission from 8.8% to 8.0% (difference: 0.7%; 95% confidence interval, 0.5-0.9) for acute myocardial infarction; 21.8% to 20.0% (difference: 1.8%; 95% confidence interval, 1.4-2.2) for heart failure; and 13.9% to 13.1% (difference: 0.8%; 95% confidence interval, 0.5-1.0) for pneumonia. Conclusions Among younger patients, readmission risk was moderately associated with hospital 30-day, risk-standardized readmission rates in elderly Medicare beneficiaries. Efforts to reduce readmissions among older patients may have important areas of overlap with younger patients, although further research may be necessary to identify specific mechanisms to tailor initiatives to younger patients.

negative: A Preliminary Assessment of Novel Coronavirus (COVID-19) Knowledge and Perceptions in Nigeria This study assessed knowledge and perceptions about COVID-19 among the general public in Nigeria during the initial week of the pandemic lockdown in the country. From March 28 to April 4, 2020, this cross-sectional survey used an anonymous online questionnaire to collect data from respondents within Nigeria. Purposive and snowball sampling techniques were used to recruit 1357 respondents, aged 15-70 years, from 180 cities and towns within Nigeria. Study data were analyzed using descriptive statistics. Approximately more than half (57.02%) of the respondents were male with a high level of education (48.86% bachelor degree or higher). Approximately half of the respondents (46.94%) opined that COVID-19 was a biological weapon designed by the Chinese government. About 94% of the respondents identified contact with airborne droplets via breathing, sneezing, or coughing as the most common mode of transmission; most respondents associated COVID-19 with coughing (81.13%), shortness of breath (73.47%) and fever (62.79%). Regular hand washing and social distancing were selected by most respondents (94.25%) as a way of preventing infection whereas 11.86% reported consuming gins, garlic, ginger, herbal mixtures and African foods/soups as preventive measures against COVID-19. The majority of the respondents (91.73%) thought COVID-19 is deadly, and most respondents (84.3%) got 4 or more answers correctly. It was also observed that the traditional media (TV/Radio) is the most common source of health information about COVID-19 (93.5%). Findings revealed that Nigerians have relatively high knowledge, mostly derived from traditional media, about COVID-19. Their perceptions of COVID-19 bear implications across public health initiatives, compliance with precautionary behavior as well as bilateral relations with foreign nations. Evidence-based campaign should be intensified to remove misconceptions and promote precautionary measures.

negative: Awareness of MERS-CoV among Staff Members of Prince Sultan Military Medical City in Riyadh, Saudi Arabia Background The Middle East respiratory syndrome coronavirus (MERS-CoV) developed infections that caused serious epidemics. Special priority of awareness and prompt initiative involvement of health workers (HW) during such intensified health situation necessitated an assessment of their preparedness, appropriate attitudes and protective strategies for better efficiency modes and acceleration during emergency. Methods HW of Prince Sultan Military Medical city in Riyadh, Saudi Arabia were reviewed through specifically designed questionnaires to acquire the demanded data. It included clinical and demographic information about the viral diseases, associated signs and symptoms, transmission and protection, and attitudes about the MERS-CoV disease. Results The study was accomplished between August and November, 2017 and 477 participants of the medical city, successfully completed the study questionnaire (Appendix I). Females represented a majority and there was an indirectly proportional decrease with the increasing age. Gradual educational increase levels reflected dominance of the university degree holders. Jobs were dominated by nurses and non-Saudis were a majority whilst, the highly experienced, (>10 years) were a minority. A majority recognized the viral transmission methods, popular information sources of MERS-CoV and associated medical terms. Highest scores were observed in dealing with protective aids and recognizing symptoms of disease. High adherence to hand hygiene protocols and correct washing steps were recorded. Correct and high levels were observed in taking preventive measures and avoiding infection. Participants responded correctly to negative and wrong actions that patients should refrain from. High scores were observed in taking appreciable attitudes towards oneself and towards others. Conclusions Expatriates were majority and nurses were dominant which, necessitates Saudization of this sector. Ministry of health pamphlets and seminars were of less impact in invigilating HW, hence, more attention and efforts are demanded. HW were quite aware of the basic and emergent health policies during epidemic episodes of MERS-CoV.

negative: COVID-19 Modelling: the Effects of Social Distancing The purpose of this article is to reach all those who find it difficult to become well informed about the repercussions of a lockdown strategy to tackle the COVID-19 pandemic and to spark discussion and thought. Here we use simple stochastic simulations to evaluate different approaches taken to tackle the crisis, along with the efficiency they will hold and the number of casualties they may incur. It is clear that the less strict the social distancing the more time it will take for life to return to normal, and the more lives will be at risk. This is shown through simulations formed by an open sourced code, which allows evaluation of the outcomes from different intervention scenarios or conditions.

negative: Distinguishing between direct and indirect consequences of covid-19.

negative: Pathology and Pathogenesis of Severe Acute Respiratory Syndrome Severe acute respiratory syndrome (SARS) is an emerging infectious viral disease characterized by severe clinical manifestations of the lower respiratory tract. The pathogenesis of SARS is highly complex, with multiple factors leading to severe injury in the lungs and dissemination of the virus to several other organs. The SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage. Several organs/cell types may be infected in the course of the illness, including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells, and certain organs may suffer from indirect injury. Extensive studies have provided a basic understanding of the pathogenesis of this disease. In this review we describe the most significant pathological features of SARS, explore the etiological factors causing these pathological changes, and discuss the major pathogenetic mechanisms. The latter include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, direct infection of immune cells, direct viral cytopathic effects, down-regulation of lung protective angiotensin converting enzyme 2, autoimmunity, and genetic factors. It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.

negative: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study As of February 20, 2020, the 2019 novel coronavirus (renamed to COVID-19) spread to 30 countries with 2130 deaths and more than 75500 confirmed cases. COVID-19 is being compared to the infamous SARS coronavirus, which resulted, between November 2002 and July 2003, in 8098 confirmed cases worldwide with a 9.6% death rate and 774 deaths. Though COVID-19 has a death rate of 2.8% as of 20 February, the 75752 confirmed cases in a few weeks (December 8, 2019 to February 20, 2020) are alarming, with cases likely being under-reported given the comparatively longer incubation period. Such outbreaks demand elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 genomes. The proposed method combines supervised machine learning with digital signal processing for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman’s rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp. Our results support a hypothesis of a bat origin and classify COVID-19 as Sarbecovirus, within Betacoronavirus. Our method achieves high levels of classification accuracy and discovers the most relevant relationships among over 5,000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.

negative: Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? PURPOSE: To evaluate the diagnostic value of computed tomography (CT) and real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) for COVID-19 pneumonia. METHODS: This retrospective study included all patients with COVID-19 pneumonia suspicion, who were examined by both CT and rRT-PCR at initial presentation. The sensitivities of both tests were then compared. For patients with a final confirmed diagnosis, clinical and laboratory data, in addition to CT imaging findings were evaluated. RESULTS: A total of 36 patients were finally diagnosed with COVID-19 pneumonia. Thirty-five patients had abnormal CT findings at presentation, whereas one patient had a normal CT. Using rRT-PCR, 30 patients were tested positive, with 6 cases initially missed. Amongst these 6 patients, 3 became positive in the second rRT-PCR assay(after 2 days, 2 days and 3 days respectively), and the other 3 became positive only in the third round of rRT-PCR tests(after 5 days, 6 days and 8 days respectively). At presentation, CT sensitivity was therefore 97.2%, whereas the sensitivity of initial rRT-PCR was only 83.3%. CONCLUSION: rRT-PCR may produce initial false negative results. We suggest that patients with typical CT findings but negative rRT-PCR results should be isolated, and rRT-PCR should be repeated to avoid misdiagnosis.

negative: Otorhinolaryngologists and Coronavirus Disease 2019 (COVID-19)

negative: Global Spread of Coronavirus Disease 2019 and Malaria: An Epidemiological Paradox in the Early Stage of A Pandemic In the current work, we discovered and analyzed the epidemiological paradox between coronavirus disease 2019 (COVID-19) and malaria in the initial phase of the ongoing pandemic. From the analysis of distribution data, the endemic presence of malaria seems to protect some populations from COVID-19 outbreak, particularly in the least developed countries. In this sense, molecular and genetic variations associated with malaria (e.g., in ACE2) might play a protective role against coronavirus infection. Moreover, the mechanism of action of some antimalarial drugs, e.g., the antiviral function, suggests their potential role in the chemoprophylaxis of coronavirus epidemics, despite possible adverse effects (e.g., retinal toxicity). All these data provide important insights to understand the spreading mechanisms of COVID-19, and to direct scientific research toward the study of some currently available medications.

negative: The clinical data from 19 critically ill patients with coronavirus disease 2019: a single-centered, retrospective, observational study BACKGROUND: The objectives of this study were to analyze the clinical features of coronavirus disease 2019 (COVID-19) and evaluate the diagnosis and treatment. METHODS: A retrospective analysis of the clinical manifestation and auxiliary examination of 19 patients with COVID-19 from the Liyuan Hospital intensive care unit (ICU) between January 16, 2020 and February 20, 2020 was undertaken. RESULTS: There were 11 male and 8 female cases among the patients. The median (range) age was 73 (38–91) years. Of these patients, 8 (42.1%) had died and the median duration from ICU admission to death was 2 (interquartile range (IQR): 1–10.75) days. Seven of these 8 patients had underlying diseases. The auxiliary examination showed fever (68.4%), dry cough (15.8%), dyspnea (10.5%), and diarrhea (5.3%). All 19 cases showed ground-glass changes on chest computed tomography. Serum hypersensitive C-reactive protein (hs-CRP) and serum amylase A (SAA) were clearly increased in all of the cases. Among the 19 cases, there were 16 (84.2%) cases in which the total number of lymphocytes decreased, 12 cases (63%) had reduced liver function, and 11 cases (58%) had deviant results for fibrinogen (FIB) and D-dimer, in particular, the D-dimer level was significantly higher in the non-survivors compared with the survivors. CONCLUSION: There were more men than women among critically ill patients. All of the cases showed ground-glass changes on chest computed tomography and the vast majority of patients displayed fever and dry cough. The clinical laboratory indices change significantly, especially the D-dimer level among non-survivors.

negative: Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray Antibodies have been used for more than 100 years in the therapy of infectious diseases but a new generation of highly potent and/or broadly cross-reactive human monoclonal antibodies (sometimes referred to as ‘super-antibodies’) offers new opportunities for intervention. The isolation of these antibodies, which are often rarely induced in human infections, has primarily been achieved by large-scale screening for suitable donors and new single B cell approaches to human monoclonal antibody generation. Engineering the antibodies to improve half-life and effector functions has further augmented their in vivo activity in some cases. Super-antibodies offer promise for the prophylaxis and therapy of infections with a range of viruses, including those that are highly antigenically variable and those that are newly emerging or have pandemic potential. The next few years will be decisive in the realization of the promise of super-antibodies.

negative: Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic Abstract Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution.

negative: Comparison of risk factors for viral and nonviral asthma exacerbations

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: Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.

negative: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19 Abstract The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy. This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections. The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes. The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks. The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19. During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4.84%. The infections were more frequent among male gender with above 60 years of age. The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1.20 and growth rate index for mortality rate was 1.12. There was a positive association between the prevalence and mortality rate (R2=0.996). The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide. It is still spreading with mutable prevalence and mortality outbreak trends. The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe. However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics.

negative: What the Corona (SARS‐CoV 2) pandemic, climate change, and the biodiversity crisis teach us about human nature

negative: Time-Resolving the COVID-19 Outbreak using frequency domain analysis Difficulties assessing and predicting the current outbreak of the severe acute respiratory syndrome coronavirus 2 can be traced, in part, to the limitations of a static description of a dynamic system. Fourier transforming the time-domain data of infections and fatalities into the frequency domain makes the dynamics easily accessible. Defining a quantity like the case fatality as a spectral density allows a more sensible comparison between different countries and demographics during an ongoing outbreak. Such a case fatality informs not only how many of the confirmed cases end up as fatalities, but also when. For COVID-19, knowing this time and using the entire case fatality spectrum allows determining that an outbreak had entered a steady-state (most likely its end) about 14 days before this is obvious from time-domain data. The lag between confirmations and deaths also helps to estimate the effectiveness of contact management: The larger the lag, the less time the average confirmed person had to infect people before quarantine.

negative: Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None.

negative: Nowcasting and Forecasting the Spread of COVID-19 and Healthcare Demand In Turkey, A Modelling Study Abstract Background: A new type of coronavirus (later named Sars-Cov-2) drew attention on 31 December 2019 after the reporting of 27 unidentified pneumonia cases detected in Wuhan, China to the World Health Organization (WHO). Rapid progression of the COVID-19 pandemic has revealed the necessity of epidemic modeling studies to evaluate the course of the epidemic and its burden on the health system. This study aims to estimate the total number of infected people, evaluate the consequences of social interventions on the healthcare system and predict the expected number of cases, intensive care needs, hospitalizations and mortality rates in Turkey according to possible scenarios via the SEIR-based epidemic modeling method. Methods: This study was carried out in three dimensions. In the first, the actual number of people infected in the community has been estimated using the number of deaths in Turkey. In the second, the expected total numbers of infected people, total deaths, total hospitalizations, and intensive care unit (ICU) bed needs have been predicted in case of no intervention. In third, the distribution of the expected number of infected people and deaths, ICU and non-ICU bed needs over time has predicted based on SEIR modeling. A simulator (TURKSAS) has been developed and predictions made in 4 scenarios for Turkey. Results: According to deaths, the estimated number of infected people in Turkey on March 21 was 123,030. In the case of no intervention (1st scenario), the expected total number of infected people is 72,091,595, the total number of deaths is 445,956, the attack rate is 88.1%, the mortality ratio is 0.54%. The ICU bed capacity in Turkey is expected to exceed 4.4-fold and non-ICU bed capacity exceeds 3.21-fold. In 2nd and 3rd scenarios according to the calculations made by considering the social compliance rates of the NPIs, the value of R0 is estimated to decrease from 3 to 1.38 level. Compliance with NPIs makes a 94,303 difference in the expected number of deaths. In both scenarios, the predicted peak value of occupied ICU and non-ICU beds remains below Turkey healthcare capacity. While this study conducted, curfew for >65 and <20 age groups were in force in Turkey. If the curfew is declared for the 21-64 age population (4th scenario), the R0 value drops below 1 (0.98), the expected deaths are 14,230 and the peak values of daily ICU and non-ICU bed demand are below the healthcare capacity. Discussion: Modeling epidemics with assumptions supported by scientific literature and establishing decision support systems based on objective criteria is an important requirement. According to scientific data for the population of Turkey, the situation is not expected to be of worse than predictions presented in the second dimension. Predictions show that 16 million people can be prevented from being infected and 100,000 deaths can be prevented by full compliance with the measures taken. Complete control of the pandemic is possible by keeping R0 below 1. For this, additional evidence-based measures are needed.

negative: Metronidazole; a Potential Novel Addition to the COVID-19 Treatment Regimen Coronavirus disease 2019 or COVID-19 has rapidly emerged as a global pandemic. This viral infection involves the upper respiratory tract and could lead to severe pneumonia with respiratory distress or even death. Certain studies have found higher initial plasma levels of most pro-inflammatory cytokines during the course of the infection. In this context, both in vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines, which are known to increase during the COVID-19 infection, including interleukin (IL)8, IL6, IL1B, tumor necrosis factor (TNF)α, IL12, IL1α, and interferon (IFN)γ, as well as the levels of C-reactive protein (CRP) and neutrophil count. Furthermore, the drug could decrease neutrophil-generated reactive oxygen species during inflammation. Metronidazole could counteract majority of the immunopathological manifestations of the COVID-19 infection. Therefore, studies with a large sample size are required to determine the efficacy of metronidazole in the treatment of COVID-19 infection.

negative: Covid-19: "Staggering number" of extra deaths in community is not explained by covid-19.

negative: Covid‐19: Supporting nurses’ psychological and mental health At the time of writing (11th April 2020) there are 1.72 million Covid‐19 infections and 104,889 deaths worldwide. In the UK the first recorded death was on the 5th of March 2020 and in just 37 days 9,875 deaths in hospital have been recorded. The 10th of April saw the highest number of UK daily deaths (980) to date. These UK figures do not include those who died in care homes or in the community. Similar death rates have been experienced in China earlier this year (3,339) and are rising globally with particularly high death rates in the US (18,761 with over half of deaths in New York State), Italy (18,939), Spain (16,353) and France (13,197).

negative: Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang Hospital Abstract Objectives To describe the clinical characteristics of patients in a Fangcang Hospital. Methods Non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests admitted between 7 February and 12 February 2020 to Dongxihu Fangcang Hospital, which was promptly constructed because of the rapid, exponential increase in COVID-19 patients in Wuhan, China, were included; clinical course through to 22 February was recorded. Results A total of 1012 non-critically ill individuals with positive SARS-CoV-2 RT-PCR tests were included in the study. Thirty (of 1012, 3.0%) individuals were asymptomatic on admission. During hospitalization, 16 of 30 (53.3%) asymptomatic individuals developed different symptoms. Fourteen of 1012 patients (1.4%) remained asymptomatic from exposure to the end of follow up, with a median duration of 24 days (interquartile range 22–27). Fever (761 of 1012, 75.2%) and cough (531 of 1012, 52.4%) were the most common symptoms. Small patchy opacities (355 of 917, 38.7%) and ground-glass opacities (508 of 917, 55.4%) were common imaging manifestations in chest CT scans. One hundred patients (9.9%) were transferred to designated hospitals due to aggravation of illness. Diarrhoea emerged in 152 of 1012 patients (15.0%). Male, older age, diabetes, cardiovascular diseases, chills, dyspnoea, So 2 value of ≤93%, white blood cell counts of >10 × 109/L and large consolidated opacities on CT images were all risk factors for aggravation of illness. Conclusions Non-critically ill individuals had different clinical characteristics from critically ill individuals. Asymptomatic infections only accounted for a small proportion of COVID-19. Although with a low incidence, diarrhoea was observed in patients with COVID-19, indicating the possibility of faecal–oral transmission.

negative: Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases Abstract Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated—Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation—public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.

negative: A crisis for elderly with mental disorders: Relapse of symptoms due to heightened anxiety due to COVID-19

negative: Social Dimensions of COVID-19 in South Africa: A Neglected Element of the Treatment Plan

negative: Spread of the Novel Coronavirus (SARS-CoV-2): Modeling and Simulation of Control Strategies The coronavirus disease 2019 (COVID-19) is spreading throughout the world and all healthcare systems are loaded beyond its capacity. The virus is named as SARS-CoV-2. In this situation, rational decisions need to be made on how the care is provided for patients with COVID-19. The Incidence report, general symptoms and readily available testing kits, different control strategies, the basic compartmental model, and some of the current research on the epidemiology of the disease are discussed and previously published models are reviewed. Modeling this disease helps in understanding the spread, and predict its future to evaluate different control strategies (Social Distancing, Contact Tracing and Hospitalization). Compartmental modeling framework is used in this work. The non-linear equations are formulated and fitted to the cumulative case and mortality data. Analytical analysis along with uncertainty analysis and sensitivity analysis is performed, and the conditions to achieve disease free equilibrium is evaluated. Finally, Different control strategies are simulated to show their importance. This paper aims to shows the advantage of mathematical modeling and their simulations in times like now, during which the COVID-19 spreading like wildfire. It also includes Pre-symptomatic and asymptomatic individuals in the modeling. The simulations are performed for the model fit to Cumulative Case and Mortality data in the United States of America. The Reproduction number is found to be 2.71914.

negative: Forecasting the novel coronavirus COVID-19 What will be the global impact of the novel coronavirus (COVID-19)? Answering this question requires accurate forecasting the spread of confirmed cases as well as analysis of the number of deaths and recoveries. Forecasting, however, requires ample historical data. At the same time, no prediction is certain as the future rarely repeats itself in the same way as the past. Moreover, forecasts are influenced by the reliability of the data, vested interests, and what variables are being predicted. Also, psychological factors play a significant role in how people perceive and react to the danger from the disease and the fear that it may affect them personally. This paper introduces an objective approach to predicting the continuation of the COVID-19 using a simple, but powerful method to do so. Assuming that the data used is reliable and that the future will continue to follow the past pattern of the disease, our forecasts suggest a continuing increase in the confirmed COVID-19 cases with sizable associated uncertainty. The risks are far from symmetric as underestimating its spread like a pandemic and not doing enough to contain it is much more severe than overspending and being over careful when it will not be needed. This paper describes the timeline of a live forecasting exercise with massive potential implications for planning and decision making and provides objective forecasts for the confirmed cases of COVID-19.

negative: Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2 The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.

negative: Forensic Histopathology Forensic histopathology is the application of histological techniques and examination to forensic pathology practice. It is a unique and specialised aspect of pathology practice. This chapter highlights several differences in forensic histopathology practice compared to clinical and surgical histopathology practice. The various roles of microscopic tissue examination in forensic pathology practice are categorised and discussed. These are in relation to definitive pathological diagnosis, confirmation of equivocal and occult pathology, serving as a form of permanent record, and providing invaluable material for education and research. Case examples are included to illustrate the impact of routine histological examinations, special stain techniques, as well as immunohistochemistry where appropriate, towards relevant pathological diagnoses, which may or may not be directly relevant to the establishment of the cause of death. Lastly, the chapter also aims to highlight some recent advances as well as the challenges ahead in this field.

negative: Biological Warfare: Infectious Disease and Bioterrorism The term biological warfare typically conjures images of medieval warriors tossing dead cattle over city walls or clandestine government agents secretly releasing mysterious microbes into enemy territory. Of course, biological warfare does encompass such activity, but the vast majority of what constitutes biological warfare is far more mundane. Ever since life evolved on earth about 3.8 billion years ago, organisms have constantly devised new ways to kill each other. Any organism that makes use of toxins—from bacteria to snakes—is engaging in a form of biological warfare. Humans who engage in biological warfare do so by taking advantage of these toxin-producing organisms.

negative: Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCoV, in the nasal tissue A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. WHO decides to determine a Public Health Emergency of International Concern (PHEIC) of 2019-nCoV. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-Cov. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 RNA expression profile in the tissues at different locations of the respiratory tract. The result indicates that the ACE2 expression appears in nasal epithelial cells. We found that the size of this population of ACE2-expressing nasal epithelial cells is comparable with the size of the population of ACE2-expression type II alveolar cells (AT2) in the Asian sample reported by Yu Zhao et al. We further detected 2019-nCoV by polymerase chain reaction (PCR) from the nasal-swab and throat-swab of seven suspected cases. We found that 2019-nCoV tends to have a higher concentration in the nasal-swab comparing to the throat-swab, which could attribute to the ACE2-expressing nasal epithelial cells. We hope this study could be informative for virus-prevention strategy development, especially the treatment of nasal mucus.

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: Maladies respiratoires, allergies et infections à COVID-19. Premières nouvelles de Wuhan

negative: Merit of an ursodeoxycholic acid clinical trial in COVID-19 patients Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, “China Promotes Bear Bile as Coronavirus Treatment”. Bear bile is rich in UDCA, comprising up to 40–50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration.

negative: Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities. DATA AND METHODS: This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities. CONCLUSION: Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.

negative: 3D Tomographic Pattern Synthesis for Enhancing the Quantification of COVID-19 The Coronavirus Disease (COVID-19) has affected 1.8 million people and resulted in more than 110,000 deaths as of April 12, 2020. Several studies have shown that tomographic patterns seen on chest Computed Tomography (CT), such as ground-glass opacities, consolidations, and crazy paving pattern, are correlated with the disease severity and progression. CT imaging can thus emerge as an important modality for the management of COVID-19 patients. AI-based solutions can be used to support CT based quantitative reporting and make reading efficient and reproducible if quantitative biomarkers, such as the Percentage of Opacity (PO), can be automatically computed. However, COVID-19 has posed unique challenges to the development of AI, specifically concerning the availability of appropriate image data and annotations at scale. In this paper, we propose to use synthetic datasets to augment an existing COVID-19 database to tackle these challenges. We train a Generative Adversarial Network (GAN) to inpaint COVID-19 related tomographic patterns on chest CTs from patients without infectious diseases. Additionally, we leverage location priors derived from manually labeled COVID-19 chest CTs patients to generate appropriate abnormality distributions. Synthetic data are used to improve both lung segmentation and segmentation of COVID-19 patterns by adding 20% of synthetic data to the real COVID-19 training data. We collected 2143 chest CTs, containing 327 COVID-19 positive cases, acquired from 12 sites across 7 countries. By testing on 100 COVID-19 positive and 100 control cases, we show that synthetic data can help improve both lung segmentation (+6.02% lesion inclusion rate) and abnormality segmentation (+2.78% dice coefficient), leading to an overall more accurate PO computation (+2.82% Pearson coefficient).

negative: Emergency department COVID management policies: one institution's experience and lessons learned. Coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, originated in Wuhan, Hubei Province, China in late 2019 and grew rapidly into a pandemic. As of the writing of this monograph, there are over 2 million confirmed cases worldwide and 147,000 deaths. New York City, with over 120,000 COVID-19-positive patients and over 11,000 deaths, has become the infection epicenter in the United States. The Mount Sinai Health System, with 8 hospitals spread across New York City and Long Island, has been on the forefront of the pandemic. This compendium summarizes the lessons learned through interdisciplinary collaborations to meet the varied challenges created by the explosive appearance of the infection in our community, and will be updated continuously as new research and best practices emerge. It is our hope is that the collaborations and lessons learned that went into creating these guidelines and protocols can serve as a useful template for other systems to adapt to their fight against COVID-19.

negative: Mortality of the COVID-19 outbreak in Sweden in relation to previous severe disease outbreaks Influenza viruses have caused disease outbreaks in human societies for a long time. Influenza often has rapid onset and relatively short duration, both in the individual and in the population. The case fatality rate varies for different strains of the virus, as do the effects on total mortality. Outbreaks related to coronavirus infections have recently become a global concern but much less is known about the dynamics of these outbreaks and their effects on mortality. In this work, disease outbreaks in Sweden, in the time period of 1860-2020, are characterized and compared to the currently ongoing COVID-19 outbreak. The focus is on outbreaks with a sharp increase in all-cause mortality. Outbreak onset is defined as the time point when deaths counts starts to increase consistently for a period of 10 days. The duration of the outbreak is defined as the time period in which mortality rates are elevated. Excess mortality is estimated by standard methods. In total there were 15 outbreaks detected in the time period, the first 14 were likely caused by influenza virus infections, the last by SARS-CoV-2. The mortality dynamics of the SARS-CoV-2 outbreak is shown to be similar to outbreaks due to influenza virus, and in terms of the number of excess deaths, might become the worst outbreak since the 'Spanish flu' of 1918-1919.

negative: Risks of Novel Coronavirus Disease (COVID-19) in Pregnancy; a Narrative Review INTRODUCTION: The outbreak of the new Coronavirus in China in December 2019 and subsequently in various countries around the world has raised concerns about the possibility of vertical transmission of the virus from mother to fetus. The present study aimed to review published literature in this regard. METHODS: In this narrative review, were searched for all articles published in various databases including PubMed, Scopus, Embase, Science Direct, and Web of Science using MeSH-compliant keywords including COVID-19, Pregnancy, Vertical transmission, Coronavirus 2019, SARS-CoV-2 and 2019-nCoV from December 2019 to March 18, 2020 and reviewed them. All type of articles published about COVID-19 and vertical transmission in pregnancy were included. RESULTS: A review of 13 final articles published in this area revealed that COVID-19 can cause fetal distress, miscarriage, respiratory distress and preterm delivery in pregnant women but does not infect newborns. There has been no report of vertical transmission in pregnancy, and it has been found that clinical symptoms of COVID-19 in pregnant women are not different from those of non-pregnant women. CONCLUSION: Overall, due to lack of appropriate data about the effect of COVID-19 on pregnancy, it is necessary to monitor suspected pregnant women before and after delivery. For confirmed cases both the mother and the newborn child should be followed up comprehensively.

negative: Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020 SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.

negative: Pneumonia Abstract Pneumonia remains the main cause of morbidity and mortality from infectious diseases in the world. The important reason for the increased global mortality is the impact of pneumonia on chronic diseases especially in the elderly population and the virulence factors of the causative microorganisms. Because elderly individuals present with comorbidities, particular attention should be paid for multidrug-resistant pathogens. Streptococcus pneumoniae remains the most frequently encountered pathogen. Enteric gram-negative rods, as well as anaerobes, should be considered in patients with aspiration pneumonia. Interventions for modifiable risk factors will reduce the risk of this infection. The adequacy of the initial antimicrobial therapy and determination of patients’ follow-up place is a key factor for prognosis. Also, vaccination is one of the most important preventive measures. In this section it was focused on several aspects, including the atypical presentation of pneumonia in the elderly, the methods to evaluate the severity of illness, the appropriate take care place and the management with prevention strategies.

negative: Recent advances of therapeutic targets and potential drugs of COVID-19. Since December 2019, numerous cases of coronavirus disease 2019 (COVID-19) caused by the infection of the novel coronavirus (2019-nCoV) have been confirmed in Wuhan, China. The outbreak of 2019-nCoV in China embodied a significant and urgent threat to global health. 2019-nCoV was a new, highly contagious coronavirus discovered following the outbreak of SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV). The novel coronavirus can cause severe respiratory disease and even death. However, no specific therapeutic drugs have been developed clinically thus far. This article examines the potential of therapeutic drugs by assessing the structure of 2019-nCoV, its mechanism in invading host cells, and the anti-viral mechanism of the human autoimmune system. We also review the latest research regarding the progress of potential therapeutic drugs and provide references for new drug developments of COVID-19.

negative: Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.

negative: Death in the era of the COVID-19 pandemic

negative: A seven-day cycle in COVID-19 infection and mortality rates: Are inter-generational social interactions on the weekends killing susceptible people? We observed a significant seven-day cycle in (i) reported COVID-19 new casesa (in 7/12 countries), and in (ii) reported COVID-19 deathsb (in 7/12 countries), based on data from the 12 developed North-American and European countries that reported more than 1,000 deaths by April 28th (Spaina, Italya and Switzerlanda, Belgiumb, Canadab and the USAb, Germanya,b, the Netherlandsa,b, Swedena,b and the UKa,b). Daily reported numbers (March 29th to April 28th) are based on Our World in Data database (derived from the European Center for Disease Control and Prevention, ECDC). In all seven countries, numbers of new cases peaked on Thursday-Friday, five days after the weekend, corresponding with a reported ~5-day lag between contact with an infected person and the manifestation of clinical symptoms. Death tolls peaked on Wednesday-Thursday in all seven countries, ~12-14 days following a weekend, corresponding with the reported median of 14-day hospitalization before death. One may suspect that the weekend restricts the availability of testing or reporting of new cases, that are eventually reported during the following week. However, to completely account for both observations, this artifact should occur uniformly in all the above-mentioned countries and consistently along the entire month studied. Moreover, deaths are defined events and seems less likely to be recorded or reported inaccurately, at least for the vast majority of cases. Thus, we hypothesize that an increase in inter-generational social interactions occurs during the weekend, which facilitates transfer of COVID-19 from younger people to older vulnerable individuals. These and additional infected older people account for most recognized COVID-19 cases and deaths, which may occur at regular time intervals, specifically in this vulnerable population. Additional explanations may include weekly rhythms in immune functions, hospital care quality, or other various health-related behaviors. Our hypotheses should be re-tested and refined based on databases that accurately report events times when these will become available.

negative: A scaling approach to estimate the COVID-19 infection fatality ratio from incomplete data SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the 'universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82% in Italy, to 0.62% in China or even 0.14% in middle Africa.

negative: Cremation based estimates suggest significant under- and delayed reporting of COVID-19 epidemic data in Wuhan and China Background: Epidemiological data provide important information for decision making. COVID-19 statistics from China fall outside of recognized and accepted medical norms. As the epicenter of the COVID-19 initial outbreak, the epidemiological information from Wuhan affects the response and preparation of other parts of China and rest of the world. Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on medical literature from China, official and non-official Chinese data sources. Methods: Data sources included literature on COVID-19 in China, official Chinese government figures, state-run and non state-run media reports. Our estimates are based on investigative media reports of crematory operations in Wuhan, which is considered as a common data end point to life. A range of estimates is presented by an exponential growth rate model from lockdown (Jan 23,2020) until the intervention started to show effects, which was estimated 14.5 days after lockdown. Results: For the cumulative infections and total deaths, under different assumptions of death rates (from 2.5% to 10%) and doubling time 6.4 days, the estimates projected on February 7, 2020 in Wuhan range from 305,000 to 1,272,000 for infections and from 6,811 to 7,223 for deaths - on the order of at least 10 times the official figures (13,603 and 545). The implied starting time of the outbreak is October 2019. Under the assumption of the official 3.14% death rate and doubling time of 2.54 days (which was derived based on Chinese official data), the infection cases reached 2.2 million on February 7. The estimates of cumulative deaths, based on both funeral urns distribution and continuous full capacity operation of cremation services up to March 23, 2020, give results around 36,000, more than 10 times of the official death toll of 2,524. Conclusions: Our study indicates a significant under-reporting in Chinese official data on the COVID-19 epidemic in Wuhan. The magnitude of discrepancy between our estimates based on cremation related data and Chinese official figures in early February, the critical time for response to the COVID-19 pandemic, suggests the need to reevaluate official statistics from China and consider all available and reasonable data sources for a better understanding of the COVID-19 pandemic.

negative: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus BACKGROUND: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. METHODS: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R(0)) from the RP model to assess the transmissibility of the SARS-CoV-2. RESULTS: The value of R(0) was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. CONCLUSIONS: Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

negative: Physician deaths from corona virus (COVID-19) disease BACKGROUND: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. AIMS: We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHODS: On 15 April 2020, a Google internet search was performed using the keywords 'doctor', 'physician', 'death', 'COVID' and 'coronavirus' in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. RESULTS: We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2% were infectious disease specialists (4/254), 6% were dentists (16/254), 4% were ENT (9/254) and 3% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44%), Iran (43/278; 15%), Philippines (21/278; 8%), Indonesia (17/278; 6%), China (16/278; 6%), Spain (12/278; 4%), USA (12/278; 4%) and UK (11/278;4%). CONCLUSIONS: Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.

negative: The First Wave of COVID-19 in Israel - Initial Analysis of Publicly Available Data The first case of COVID-19 was confirmed in Israel on February 21, 2020. Within approximately 30 days, the total number of confirmed cases climbed up to 1,000, accompanied by a doubling period of less than 3 days. About one week later, after this number exceeded 4,000 cases, and following some extremely strict measures taken by the Israeli government, the daily detection rate started a sharp decrease from the peak value of 1,131 down to slightly more than 100 new confirmed cases on April 30. Motivated by this encouraging data, similar to the trends observed in many other countries, along with the growing economic pressures, the Israeli government started relaxing its emergency regulations as part of an "exit strategy". This article attempts to analyze the currently available data on Israel and a country of similar size (Sweden) in order to understand the local dynamics of COVID-19, assess the effect of the implemented intervention measures, and discuss some plausible scenarios for the foreseeable future.

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: Structural disorder in the proteome and interactome of Alkhurma virus (ALKV) Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different host systems. Furthermore, the ability of viruses to efficiently adjust and accommodate to their hostile habitats is also intrinsic disorder-dependent. However, little is currently known on the level of penetrance and functional utilization of intrinsic disorder in the ALKV proteome. To fill this gap, we used here multiple computational tools to evaluate the abundance of intrinsic disorder in the ALKV genome polyprotein. We also analyzed the peculiarities of intrinsic disorder predisposition of the individual viral proteins, as well as human proteins known to be engaged in interaction with the ALKV proteins. Special attention was paid to finding a correlation between protein functionality and structural disorder. To the best of our knowledge, this work represents the first systematic study of the intrinsic disorder status of ALKV proteome and interactome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-018-2968-8) contains supplementary material, which is available to authorized users.

negative: Management of septic shock and severe infections in migrants and returning travelers requiring critical care During the past decade, global human movement created a virtually “borderless world”. Consequently, the developed world is facing “forgotten” and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them.

negative: Chapter 3 Measuring, Monitoring, and Evaluating the Health of a Population Abstract Public health depends on information derived from monitoring population health status to identify community health problems, and to diagnose and investigate health problems and hazards in the community. These depend on vital statistics and disease reporting systems, including for non-communicable diseases, injuries, risk factors, health care resources, utilization of resources, and special disease registries such as for cancer, birth defects, and many others. Information technology and computerization allow data systems to be linked to assess the impact of health conditions and utilization of services providing vital information for epidemiological and economic analyses for policy development. Epidemiology and its associated quantitative disciplines of biostatistics and demography are augmented by social and behavioral qualitative research methods. The disciplines of health systems research provide evidence from population health monitoring crucial to policy and priority determination. This introductory chapter is augmented in subsequent chapters, and by specialized courses in public health education programs.

negative: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

negative: Pneumonia Caused by Emerging Viral Agents Emerging viruses that cause pneumonia in humans are agents which normally circulate in the animal population but can move to human hosts under certain circumstances, which determines the occurrence of a new type of disease. The Middle East respiratory syndrome (MERS) is caused by a coronavirus. The disease has a wide symptomatic spectrum that can range from asymptomatic infections to fulminant respiratory failure. Diagnostic confirmation is achieved through viral isolation. Severe acute respiratory syndrome (SARS), also produced by a coronavirus, is capable of producing a serious pulmonary disease outbreak with no reappearance. The clinical presentation includes fever, malaise, cough, and headache followed by diarrhea. Other coronaviruses (HCoV-NL63 and HCoV-HKU1) can cause serious lower respiratory infections in small children, the elderly, and immunosuppressed patients. Influenza virus is widespread in nature, and avian virus may spread to humans, as has been reported with H7N9, H5N1, H10N8, and H6N1. Cardiopulmonary hantavirus syndrome, a feverish disease characterized by respiratory insufficiency and shock, is produced by Andes virus. Other emerging viruses are enterovirus D68 and polyomavirus.

negative: Answering the right questions for policymakers on COVID-19

negative: Identifying baseline clinical features of people with COVID-19 Objectives: To describe baseline clinical characteristics of adult patients with COVID-19. Methods: We conducted a scoping review of the evidence available at LitCovid, until March 23th, 2020, and selected articles that reported the prevalence of socio-demographic characteristics, symptoms and co-morbidities in adults with COVID-19. Results: In total, 1 572 publications were published on LitCovid. We have included 56 articles in our analysis, with 89% conducted in China, and 75% contained inpatients. Three studies were conducted in North America and one in Europe. Participants age ranged from 28 to 70 years, with balanced gender distribution. Proportion of asymptomatic cases were from 2 to 79%. The most common reported symptoms were fever [4-99%], cough [4-92%], dyspnoea/shortness of breath [1-90%], fatigue 4-89%], myalgia [3-65%], and pharyngalgia [2-61%], while regarding co-morbidities we found cardiovascular disease [1-40%], hypertension [0-40%] and cerebrovascular disease [1-40%]. Such heterogeneity impairs the conduction of meta-analysis. Conclusions: The infection by COVID-19 seems to affect people in a very diverse manner and with different characteristics. With the available data it is not possible to clearly identify those at higher risk of being infected with this condition. Furthermore, the evidence from countries other than China is, at the day, too scarce.

negative: Reisemedizin Tauchgebiete befinden sich oft in exotischen, subtropischen oder tropischen Gebieten. Der Taucherarzt sollte neben Ratschlägen zum Tauchen auch Information über Krankheiten und deren Prophylaxe vermitteln.

negative: Risk assessment of novel coronavirus COVID-19 outbreaks outside China We developed a computational tool to assess the risk of novel coronavirus outbreaks outside China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia and Europe, and we investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.

negative: Aggregated Private Information Retrieval: A First Practical Implementation to Support Large-Scale Disease Analytics With the outbreak of the coronavirus, governments rely more and more on location data shared by European mobile network operators to monitor the advancements of the disease. In order to comply with often strict privacy requirements, this location data, however, has to be anonymized, limiting its usefulness for making statements about a filtered part of the population, like already infected people. In this research, we aim to assist with the disease tracking efforts by designing a protocol to detect coronavirus hotspots from mobile data while still maintaining compliance with privacy expectations. We use various state-of-the-art privacy-preserving cryptographic primitives to design a protocol that can best be described as aggregated private information retrieval (APIR). Our protocol is based on homomorphic encryption, with additional measures to protect against malicious requests from clients. We have implemented our APIR protocol in the SEAL library and tested it for parameters suitable to create a coronavirus hotspot map for entire nationstates. This demonstrates that it is feasible to apply our APIR protocol to support nationwide disease analysis while still preserve the privacy of infected people.

negative: COVID-19 excess deaths in the United States during April 2020 Background: Some have claimed that the number of COVID-19 deaths is not much greater than would be experienced in the usual course of events. We sought to estimate the number of deaths due to COVID-19 in the United States during April 2020 and compare that to the number of expected deaths in the same time period. Methods: The Institute for Health Metrics and Evaluation (IHME) predicts that 67,212 COVID-19 deaths will occur during April 2020. To obtain the number of excess COVID-19 deaths, we multiplied published infection fatality rates by age by population numbers to obtain assumed infection rates. We then subtracted the expected number of deaths calculated using life table mortality rates. Results: During April 2020 there may be 61,690 to 62,526 excess deaths. Population infection rates of 3.6% to 4.3% by mid-April 2020 would generate the number of COVID-19 deaths predicted by IHME. Conclusions: During April 2020 over 90% of the COVID-19 deaths can be classified as excess deaths. These deaths would normally occur over 11.2 to 13.3 months instead of being concentrated in 1 month.

negative: Pursuing a Good Death in the Time of COVID-19

negative: COVID‐19 and rationally layered social distancing I would like to thank Dr. Thomson for the very pertinent and relevant points that he raised in his thoughtful letter Where are we now with COVID-19? [1]. As my response will illustrate, and in what probably will become a defining feature of conversations surrounding COVID-19 for quite some time, attempts to answer will only make room for more questions. As COVID-19 is unfolding, every day is marked by novel developments. Since the editorial went to press [2], the outbreak has expanded considerably. Over 128,000 individuals were infected worldwide as of March 13, 2020, leading to 4720 deaths [3]. In early March, while the outbreak in China appeared to start to subside [4], it started to amplify in Europe and the United States. The first fatality in the United States occurred on February 29, 2020 in a suburb of Seattle. On March 4m the first death was reported outside WA state, in CA, and was the 11th death in the United States. On March 6, the first two fatalities were reported in Florida. On March 11, 2020, the World Health Organization declared the outbreak a pandemic [5].

negative: Covid-19: Supporting nurses' psychological and mental health

negative: Positional Bias of MHC Class I Restricted T-Cell Epitopes in Viral Antigens Is Likely due to a Bias in Conservation The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells. It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days. The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. One potential source of DRiPs is premature translation termination. If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus. By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus. Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource. We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented. Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation.

negative: Mobility traces and spreading of COVID-19 We use human mobility models, for which we are experts, and attach a virus infection dynamics to it, for which we are not experts but have taken it from the literature, including recent publications. This results in a virus spreading dynamics model. The results should be verified, but because of the current time pressure, we publish them in their current state. Recommendations for improvement are welcome. We come to the following conclusions: 1. Complete lockdown works. About 10 days after lockdown, the infection dynamics dies down. This assumes that lockdown is complete, which can be guaranteed in the simulation, but not in reality. Still, it gives strong support to the argument that it is never too late for complete lockdown. 2. As a rule of thumb, we would suggest complete lockdown no later than once 10% of hospital capacities available for COVID-19 are in use, and possibly much earlier. This is based on the following insights: a. Even after lockdown, the infection dynamics continues at home, leading to another tripling of the cases before the dynamics is slowed. b. There will be many critical cases coming from people who were infected before lockdown. Because of the exponential growth dynamics, their number will be large. c. Researchers with more detailed disease progression models should improve upon these statements. 3. Our simulations say that complete removal of infections at child care, primary schools, workplaces and during leisure activities will not be enough to sufficiently slow down the infection dynamics. It would have been better, but still not sufficient, if initiated earlier. 4. Infections in public transport play an important role. In the simulations shown later, removing infections in the public transport system reduces the infection speed and the height of the peak by approximately 20%. Evidently, this depends on the infection parameters, which are not well known. -- This does not point to reducing public transport capacities as a reaction to the reduced demand, but rather use it for lower densities of passengers and thus reduced infection rates. 5. In our simulations, removal of infections at child care, primary schools, workplaces, leisure activities, and in public transport may barely have been sufficient to control the infection dynamics if implemented early on. Now according to our simulations it is too late for this, and (even) harsher measures will have to be initiated until possibly a return to such a restrictive, but still somewhat functional regime will again be possible. Evidently, all of these results have to be taken with care. They are based on preliminary infection parameters taken from the literature, used inside a model that has more transport/movement details than all others that we are aware of but still not enough to describe all aspects of reality, and suffer from having to write computer code under time pressure. Optimally, they should be confirmed independently. Short of that, given current knowledge we believe that they provide justification for "complete lockdown" at the latest when about 10% of available hospital capacities for COVID-19 are in use (and possibly earlier; we are no experts of hospital capabilities). What was not investigated in detail in our simulations was contact tracing, i.e. tracking down the infection chains and moving all people along infection chains into quarantine. The case of Singapore has so far shown that this may be successful. Preliminary simulation of that tactic shows that it is difficult to implement for COVID-19, since the incubation time is rather long, people are contagious before they feel sick, or maybe never feel sufficiently sick at all. We will investigate in future work if and how contact tracing can be used together with a restrictive, but not totally locked down regime. When opening up after lockdown, it would be important to know the true fraction of people who are already immune, since that would slow down the infection dynamics by itself. For Wuhan, the currently available numbers report that only about 0.1% of the population was infected, which would be very far away from "herd immunity". However, there have been and still may be many unknown infections.

negative: Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2 The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020 Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020 Literature searches were performed using keywords including “Coronavirus 2019”, “2019-nCoV”, “COVID-19”, and “SARS-CoV-2” Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening After full-text review, 37 articles were eligible to include in our study Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO) The case fatality rate in patients infected with SARC-CoV-2 is 4 3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension The mortality rate in healthy subjects is less than 1% Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures

negative: When health professionals look death in the eye: the mental health of professionals who deal daily with the 2019 coronavirus outbreak Abstract Background : The fact that COVID-19 is transmissible from human to human and associated with high morbidity and potentially fatality can intensify the perception of personal danger. In addition, the foreseeable shortage of supplies and an increasing flow of suspected and real cases of COVID-19 contribute to the pressures and concerns of health professionals. Method : The studies were identified in well-known international journals found in two electronic databases: Scopus and Embase. The data were cross-checked with information from the main international newspapers. Results : Work-related stress is a potential cause of concern for health professionals. It has been associated with anxiety including multiple clinical activities, depression in the face of the coexistence of countless deaths, long work shifts with the most diverse unknowns and demands in the treatment with patients with COVID-19. Therefore, it is an important indicator of psychic exhaustion. Conclusions : As coronavirus cases increase and deaths surge in Italy, new figures show an "enormous" level of contagion among the country's medical personnel. At least 2,629 health workers have been infected with coronavirus since the outbreak onset in February, representing 8.3% of total cases. The percentage of infected health workers has almost doubled the number registered in China throughout the epidemic. Intensive care unit physicians are on their stress limit, especially when dealing with older patients and with death prospects. Doctors, not a relative, are inevitably the last people a dying COVID-19 patient will see.

negative: The COVID-19 response for vulnerable people in places affected by conflict and humanitarian crises

negative: The Postdigital in Pandemic Times: a Comment on the Covid-19 Crisis and its Political Epistemologies

negative: Potential lethal outbreak of coronavirus disease (COVID-19) among the elderly in retirement homes and long-term facilities, France, March 2020 Motivated by the potential devastating effect of a COVID-19 outbreak in retirement homes and long-term facilities for dependent elderly, we present the impact of worst-case scenarios in French institutions using a specific age structure and case–age fatality ratios. The death toll could equal the yearly death toll caused by seasonal influenza in those older than 65 years or could largely exceed that, depending on the final attack rate and proportion of infected institutions.

negative: Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020 On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections’ timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5–20.2%). Most infections occurred before the quarantine start.

negative: Explaining the Bomb-Like Dynamics of COVID-19 with Modeling and the Implications for Policy Using a Bayesian approach to epidemiological compartmental modeling, we demonstrate the bomb-like behavior of exponential growth in COVID-19 cases can be explained by transmission of asymptomatic and mild cases that are typically unreported at the beginning of pandemic events due to lower prevalence of testing. We studied the exponential phase of the pandemic in Italy, Spain, and South Korea, and found the R0 to be 2.56 (95% CrI, 2.41-2.71), 3.23 (95% CrI, 3.06-3.4), and 2.36 (95% CrI, 2.22-2.5) if we use Bayesian priors that assume a large portion of cases are not detected. Weaker priors regarding the detection rate resulted in R0 values of 9.22 (95% CrI, 9.01-9.43), 9.14 (95% CrI, 8.99-9.29), and 8.06 (95% CrI, 7.82-8.3) and assumes nearly 90% of infected patients are identified. Given the mounting evidence that potentially large fractions of the population are asymptomatic, the weaker priors that generate the high R0 values to fit the data required assumptions about the epidemiology of COVID-19 that do not fit with the biology, particularly regarding the timeframe that people remain infectious. Our results suggest that models of transmission assuming a relatively lower R0 value that do not consider a large number of asymptomatic cases can result in misunderstanding of the underlying dynamics, leading to poor policy decisions and outcomes.

negative: Opportunistic Infections with Coronavirus-Like Particles in Patients Infected with the Human Immunodeficiency Virus? Summary From 35 patients infected with Human Immunodeficiency Virus (HIV) and belonging to various risk groups, 60 stool specimens were examined for the presence of Coronavirus-like particles (CVLP) using electron microscopy. CVLP were detected in 5 (8%) stool samples from 5 different patients (14%). Only one of the patients had diarrhoea. The five patients with CVLP-positive stools were all at advanced stages of HIV infection. The remarkable discrepancy between our data and another study, reporting a rate of 50% CVLP-positive HIV patients, most of them persistently shedding the virus, is discussed.

negative: COVID-19 Epidemic in Switzerland: Growth Prediction and Containment Strategy Using Artificial Intelligence and Big Data Using a previously developed agent-based artificial intelligence simulation platform (EnerPol) coupled with Big Data, the evolution and containment of COVID-19 in Switzerland is examined. The EnerPol platform has been used in a broad range of case studies in different sectors in all of Europe, USA, Japan, South Korea and sub Saharan Africa over the last 10 years. In the present study, the entire Swiss population (8.57 million people), including cross-border commuters, and the entire Swiss public and private transport network that is simulated to assess transmission of the COVID-19 virus. The individual contacts within the population, and possible transmission pathways, are established from a simulation of daily activities that are calibrated with micro-census data. Various governmental interventions with regards to closures and social distancing are also implemented. The epidemiology of the COVID-19 virus is based on publicly available statistical data and adapted to Swiss demographics. The predictions estimate that between 22 February and 11 April 2020, there will be 720 deaths from 83300 COVID-19 cases, and 73300 will have recovered; our preliminary variability in these estimates is about 21% over the aforementioned period. In the absence of governmental intervention, 42.7% of the Swiss population would have been infected by 25 April 2020 compared to our prediction of a 1% infection over this time period, saving thousands of lives. It is argued that future scenarios regarding relaxation of the lockdown should be carefully simulated, as by 19 April 2020, there will still remain a substantial number of infected individuals, who could retrigger a second spread of COVID-19. Through the use of a digital tool, such as Enerpol, to evaluate in a data-driven manner the impacts of various policy scenarios, the most effective measures to mitigate a spread of COVID-19 can be devised while we await the deployment of large-scale vaccination for the population globally. By tailoring the spatio-temporal characteristics of the spread to match the capacity of local healthcare facilities, appropriate logistic needs can be determined, in order not to overwhelm the health care services across the country.

negative: Structural basis for the recognition of the 2019-nCoV by human ACE2 Angiotensin-converting enzyme 2 (ACE2) has been suggested to be the cellular receptor for the new coronavirus (2019-nCoV) that is causing the coronavirus disease 2019 (COVID-19). Like other coronaviruses such as the SARS-CoV, the 2019-nCoV uses the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) to engage ACE2. We most recently determined the structure of the full-length human ACE2 in complex with a neutral amino acid transporter B0AT1. Here we report the cryo-EM structure of the full-length human ACE2 bound to the RBD of the 2019-nCoV at an overall resolution of 2.9 Å in the presence of B0AT1. The local resolution at the ACE2-RBD interface is 3.5 Å, allowing analysis of the detailed interactions between the RBD and the receptor. Similar to that for the SARS-CoV, the RBD of the 2019-nCoV is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. Pairwise comparison reveals a number of variations that may determine the different affinities between ACE2 and the RBDs from these two related viruses.

negative: Ecology of Increasing Diseases: Population Growth and Environmental Degradation The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world.

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: Advances in disease diagnosis, vaccine development and other emerging methods to control pathogens in aquaculture Disease is still regarded as a major constraint to aquaculture production globally. Rapid disease diagnosis and vaccination play a huge part in the control of bacterial diseases, and there has been significant progress in both of these areas. This chapter considers the limitations of existing methods and reviews recent advances made in pathogen detection technologies and vaccine development methodologies. Future directions are discussed, including nanotechnology and reversed vaccinology.

negative: Community-Acquired Pneumonia Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the world, with an annual incidence ranking from 1.6 to 10.6 per 1.000 people in Europe. The incidence is age related, peaking over 65 years. Up to 75 % of CAP patients with pulmonary diseases need hospitalization, and up to a 10 % of these are admitted to an intensive care unit (ICU) due to complications like sepsis, septic shock, and acute respiratory distress syndrome (ARDS) [1–3]. Up to 8 % of CAP patients die within 90 days of disease onset; 21 % die within a year [4] making CAP the most frequent cause of death from infection in Europe and the third most common cause of death in general [5]. Mortality is highest in ICU patients.

negative: Infección por coronavirus (COVID-19) en Anales de Pediatría

negative: A demographic scaling model for estimating the total number of COVID-19 infections Background: The total number of COVID-19 infections is critical information for decision makers when assessing the progress of the pandemic, its implications, and policy options. Despite efforts to carefully monitor the COVID-19 pandemic, the reported number of confirmed cases is likely to underestimate the actual number of infections. We aim to estimate the total number of COVID-19 infections in a straightforward manner using a demographic scaling approach based on life tables. Methods: We use data on total number of COVID-19 attributable deaths, population counts, and life tables as well as information on infection fatality rates as reported in Verity et al. (2020) for Hubei, China. We develop a scaling approach based on life tables and remaining life expectancy to map infection fatality rates between two countries to account for differences in their age structure, health status, and the health care system. The scaled infection fatality rates can be used in combination with COVID-19 attributable deaths to calculate estimates of the total number of infected. We also introduce easy to apply formulas to quantify the bias that would be required in death counts and infection fatality rates in order to reproduce a certain estimate of infections. Findings: Across the 10 countries with most COVID-19 deaths as of April 17, 2020, our estimates suggest that the total number of infected is approximately 4 times the number of confirmed cases. The uncertainty, however, is high, as the lower bound of the 95% prediction interval suggests on average twice as many infections than confirmed cases, and the upper bound 10 times as many. Country-specific variation is high. For Italy, our estimates suggest that the total number of infected is approximately 1 million, or almost 6 times the number of confirmed cases. For the U.S., our estimate of 1.4 million is close to being twice as large as the number of confirmed cases, and the upper bound of 3 million is more than 4 times the number of confirmed cases. For Germany, where testing has been comparatively extensive, we estimate that the total number of infected is only 1.2 times (upper bound: 3 times) than the number of confirmed cases. Comparing our results with findings from local seroprevalence studies and applying our bias formulas shows that some of their infection estimates would only be possible if just a small fraction of COVID-19 related deaths were recorded, indicating that these seroprevalence estimates might not be representative for the total population. Interpretation: As many countries lack population based seroprevalence studies, straightforward demographic adjustment can be used to deliver useful estimates of the total number of infected cases. Our results imply that the total number COVID-19 cases may be approximately 4 times (95%: 2 to 10 times) that of the confirmed cases. Although these estimates are uncertain and vary across countries, they indicate that the COVID-19 pandemic is much more broadly spread than what confirmed cases would suggest, and the number of asymptomatic cases or cases with mild symptoms may be high. In cases in which estimates from local seroprevalence studies or from simulation models exist, our approach can provide a simple benchmark to assess the quality of those estimates.

negative: Spousal bereavement, mortality and risk of negative health outcomes among older adults: a population-based study Objective: to examine whether spousal bereavement increases the risk of death and negative health outcomes and among older people. Design: cohort study and self-controlled cohort crossover study Setting: routinely collected administrative and healthcare data with individual-level linkage between several national registries in Sweden. Participants: older persons (>65 years) living in the community whose spouse died in 2013-2014, individually matched with controls. Main outcome measures: death from any cause (primary outcome), acute cardiovascular events, pneumonia, hip fracture, and intentional self-harm (secondary outcomes). In the cohort study, incidence rate ratios were estimated with conditional fixed-effect Poisson regression models adjusted for potential confounders. In the self-controlled cohort crossover study, relative incidence ratios were estimated over the 12 months before and after spousal loss with unadjusted conditional fixed-effect Poisson regression including a bereavement-by-time interaction. Results: 42 918 bereaved older spouses were included and matched to an equal number of married controls (mean age 78.9 [SD 7.2] years, 68% women). During the first year of follow-up, the risk of death from any cause was 1.66 (95% confidence interval 1.53 to 1.80) times higher for bereaved cases than for married controls, and bereaved cases survived on average 4.2 days shorter than married controls. Bereaved cases also experienced an increased risk of acute cardiovascular events (incidence rate ratio 1.34, 1.24 to 1.44), hip fracture (1.48, 1.30 to 1.68), pneumonia (1.14, 1.04 to 1.25), and self-harm (3.49, 2.11 to 5.76). These associations were strongly time-dependent, increasing sharply immediately after spousal loss and weakening as time elapsed. In the self-controlled cohort crossover study, the relative incidence ratios increased for all four secondary outcomes, starting already during the 6-month period preceding spousal loss. Conclusion: Among older persons, the association between spousal bereavement and the risk of negative health outcomes and mortality is most likely causal. Our finding that the risk of adverse health consequences increases already during the 6 months prior to spousal loss indicates that palliative care services have an important role to play in providing timely bereavement care to spouses and other family caregivers.

negative: The fiscal value of human lives lost from coronavirus disease (COVID-19) in China OBJECTIVE: According to the WHO coronavirus disease (COVID-19) situation report 35, as of 24th February 2020, there was a total of 77,262 confirmed COVID-19 cases in China. That included 2595 deaths. The specific objective of this study was to estimate the fiscal value of human lives lost due to COVID-19 in China as of 24th February 2020. RESULTS: The deaths from COVID-19 had a discounted (at 3%) total fiscal value of Int$ 924,346,795 in China. Out of which, 63.2% was borne by people aged 25–49 years, 27.8% by people aged 50–64 years, and 9.0% by people aged 65 years and above. The average fiscal value per death was Int$ 356,203. Re-estimation of the economic model alternately with 5% and 10 discount rates led to a reduction in the expected total fiscal value by 21.3% and 50.4%, respectively. Furthermore, the re-estimation of the economic model using the world’s highest average life expectancy of 87.1 years (which is that of Japanese females), instead of the national life expectancy of 76.4 years, increased the total fiscal value by Int$ 229,456,430 (24.8%).

negative: Dynamics of the COVID-19 -- Comparison between the Theoretical Predictions and Real Data A new coronavirus disease, called COVID-19, appeared in the Chinese region of Wuhan at the end of last year; since then the virus spread to other countries, including most of Europe. We propose a differential equation governing the evolution of the COVID-19. This dynamic equation also describes the evolution of the number of infected people for 13 common respiratory viruses (including the SARS-CoV-2). We validate our theoretical predictions with experimental data for Italy, Belgium and Luxembourg, and compare them with the predictions of the logistic model. We find that our predictions are in good agreement with the real world since the beginning of the appearance of the COVID-19; this is not the case for the logistic model that only applies to the first days. The second part of the work is devoted to modelling the descending phase, i.e. the decrease of the number of people tested positive for COVID-19. Also in this case, we propose a new set of dynamic differential equations that we solved numerically. We use our differential equations parametrised with experimental data to make several predictions, such as the date when Italy, Belgium, and Luxembourg will reach a peak number of SARS-CoV-2 infected people. The descending curves provide valuable information such as the duration of the COVID-19 epidemic in a given Country and therefore when it will be possible to return to normal life.

negative: Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.

negative: Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan Object Meteorological parameters are the important factors influencing the infectious diseases like severe acute respiratory syndrome (SARS). This study aims to explore the association between coronavirus disease (COVID-19) death and weather parameters. Methods In this study, we collected the daily death number of COVID-19, meteorological and air pollutant data from 20 January, 2020 to 29 February, 2020 in Wuhan, China. Then, the generalized additive model was applied to explore the impact of temperature, humidity and diurnal temperature range on daily mortality of COVID-19. Results There were in total 2299 COVID-19 mortality counts in Wuhan. A positive association with COVID-19 mortality was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, each 1 unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 mortality at lag 3. However, both per 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 mortality at lag 3 and lag 5, respectively. Conclusion In summary, this study suggests the temperature variation and humidity may be important factors affecting the COVID-19 mortality.

negative: Modelling spatial variations of coronavirus disease (COVID-19) in Africa Abstract Clinical and epidemiological evidence has been advanced for human-to-human transmission of the novel coronavirus rampaging the world since late 2019. Outliers in the human-to-human transmission are yet to be explored. In this study, we examined the spatial density and leaned statistical credence to the global debate. We constructed spatial variations of clusters that examined the nexus between COVID-19 attributable deaths and confirmed cases. We rely on publicly available data on confirmed cases and death across Africa to unravel the unobserved factors, that could be responsible for the spread of COVID-19. We relied on the dynamic system generalised method of moment estimation procedure and found a ~0.045 Covid19 deaths as a result of confirmed cases in Africa. We accounted for cross-sectional dependence and found a basis for the strict orthogonal relationship. Policy measures were discussed.

negative: Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020 Importance: Efforts to track the severity and public health impact of coronavirus disease 2019 (COVID-19) in the United States have been hampered by state-level differences in diagnostic test availability, differing strategies for prioritization of individuals for testing, and delays between testing and reporting. Evaluating unexplained increases in deaths due to all causes or attributed to nonspecific outcomes, such as pneumonia and influenza, can provide a more complete picture of the burden of COVID-19. Objective: To estimate the burden of all deaths related to COVID-19 in the United States from March to May 2020. Design, Setting, and Population: This observational study evaluated the numbers of US deaths from any cause and deaths from pneumonia, influenza, and/or COVID-19 from March 1 through May 30, 2020, using public data of the entire US population from the National Center for Health Statistics (NCHS). These numbers were compared with those from the same period of previous years. All data analyzed were accessed on June 12, 2020. Main Outcomes and Measures: Increases in weekly deaths due to any cause or deaths due to pneumonia/influenza/COVID-19 above a baseline, which was adjusted for time of year, influenza activity, and reporting delays. These estimates were compared with reported deaths attributed to COVID-19 and with testing data. Results: There were approximately 781â¯000 total deaths in the United States from March 1 to May 30, 2020, representing 122â¯300 (95% prediction interval, 116â¯800-127â¯000) more deaths than would typically be expected at that time of year. There were 95â¯235 reported deaths officially attributed to COVID-19 from March 1 to May 30, 2020. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19-reported deaths during that period. In several states, these deaths occurred before increases in the availability of COVID-19 diagnostic tests and were not counted in official COVID-19 death records. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths. Conclusions and Relevance: Excess deaths provide an estimate of the full COVID-19 burden and indicate that official tallies likely undercount deaths due to the virus. The mortality burden and the completeness of the tallies vary markedly between states.

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: Medical Ethics in Disasters Disasters frequently create demands that outstrip available existing medical and societal resources. This may be particularly problematic for giving medical care, because disasters may destroy the infrastructures necessary to both provide patients care and keep new health problems from emerging. Disaster may, for example, not only strike care providers and hospital facilities directly; they may decimate communities’ capacities to provide food to the population and carry out critical waste disposal services. All these effects may be most important to policymakers and care providers deciding triage priorities during disasters. Referring to just these two examples, food and waste disposal services, for instance, care providers should treat first not only other care providers, who can, then, take care of others, but food preparers and waste disposal personnel, likewise, to save the most lives. These two examples are just a few among many that warrant priority for this same reason.

negative: Hemagglutinating Encephalomyelitis Coronavirus Infection in Pigs, Argentina We describe an outbreak of vomiting, wasting, and encephalomyelitis syndrome in piglets in Argentina, caused by porcine hemagglutinating encephalomyelitis coronavirus (PHE-CoV) infection. Diagnosis was made by epidemiologic factors, pathologic features, immunohistochemistry, reverse transcription–PCR, and genomic sequencing. This study documents PHE-CoV infection in South America.

negative: Small Solitary Ground-Glass Nodule on CT as an Initial Manifestation of Coronavirus Disease 2019 (COVID-19) Pneumonia The 2019 novel coronavirus (2019-nCoV) outbreak in Wuhan, Hubei Province, China in 2019 led to large numbers of people being infected and developing atypical pneumonia (coronavirus disease 2019, COVID-19). Typical imaging manifestations of patients infected with 2019-nCoV has been reported, but we encountered an atypical radiological manifestation on baseline computed tomography (CT) images in three patients from Wuhan, China infected with the 2019-nCoV. Surprisingly, the only similar CT finding was a solitary sub-centimeter ground-glass nodule adjacent to bronchovascular bundles, which could be easily overlooked. In addition, the follow-up images in these patients showed how COVID-19 pneumonia evolved from these small nodules. The radiologic manifestation of the three cases will expand contemporary understanding of COVID-19.

negative: National Consumption of Antimalarial Drugs and COVID-19 Deaths Dynamics : an Ecological Study COVID-19 (Coronavirus Disease-2019) is an international public health problem with a high rate of severe clinical cases. Several treatments are currently being tested worldwide. This paper focuses on anti-malarial drugs such as chloroquine or hydroxychloroquine, which have been currently reviewed by a systematic study as a good potential candidate and that has been reported as the most used treatment by a recent survey of physicians. We compare the dynamics of COVID-19 death rates in countries using anti-malaria drugs as a treatment from the start of the epidemic versus countries that do not, the day of the 3rd death and the following 10 days. We show that the first group have a much slower dynamic in death rates that the second group. This univariate analysis is of course only one additional piece of evidence in the debate regarding the efficiency of anti-malaria drugs, and it is also limited as the two groups certainly have other systemic differences in the way they responded to the pandemic, in the way they report death or in their population that better explain differences in dynamics (systematic differences that may also explain their choice to rely on anti-malaria drugs in the first place). Nevertheless, the difference in dynamics is so striking that we believe that the urgency context commands presenting the univariate analysis before delving into further analysis. In the end, this data might ultimately be either a piece of evidence in favor or anti-malaria drugs or a stepping stone in understanding further what other ecological aspects place a role in the dynamics of COVID-19 deaths.

negative: Turning Crisis into Opportunity: Nature of Science and Scientific Inquiry as Illustrated in the Scientific Research on Severe Acute Respiratory Syndrome Interviews with key scientists who had conducted research on Severe Acute Respiratory Syndrome (SARS), together with analysis of media reports, documentaries and other literature published during and after the SARS epidemic, revealed many interesting aspects of the nature of science (NOS) and scientific inquiry in contemporary scientific research in the rapidly growing field of molecular biology. The story of SARS illustrates vividly some NOS features advocated in the school science curriculum, including the tentative nature of scientific knowledge, theory-laden observation and interpretation, multiplicity of approaches adopted in scientific inquiry, the inter-relationship between science and technology, and the nexus of science, politics, social and cultural practices. The story also provided some insights into a number of NOS features less emphasised in the school curriculum—for example, the need to combine and coordinate expertise in a number of scientific fields, the intense competition between research groups (suspended during the SARS crisis), the significance of affective issues relating to intellectual honesty and the courage to challenge authority, the pressure of funding issues on the conduct of research and the ‘peace of mind’ of researchers, These less emphasised elements provided empirical evidence that NOS knowledge, like scientific knowledge itself, changes over time. They reflected the need for teachers and curriculum planners to revisit and reconsider whether the features of NOS currently included in the school science curriculum are fully reflective of the practice of science in the 21st century. In this paper, we also report on how we made use of extracts from the news reports and documentaries on SARS, together with episodes from the scientists’ interviews, to develop a multimedia instructional package for explicitly teaching the prominent features of NOS and scientific inquiry identified in the SARS research.

negative: The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals

negative: Infektionsschutz und spezielle Hygienemaßnahmen in klinischen Disziplinen

negative: A National Strategy for Ventilator and ICU Resource Allocation During the COVID-19 Pandemic

negative: Are your IT staff ready for the pandemic-driven insider threat? As this article is being written it's mid-March. The situation likely will have changed significantly by the time you read this, as it does by the day and even the hour. The World Health Organisation (WHO) has declared Covid-19 to be a global pandemic and the UK Government has stepped up its response from the ‘contain’ to the ‘delay’ phase. Public spaces and transport are noticeably quieter and many workplaces are getting emptier as staff members work from home. The Covid-19 pandemic and consequent lockdowns are hitting businesses hard. And as workforces move to remote working, IT departments are under pressure. At the same time, cyber criminals are exploiting the pandemic, with rises in phishing and other forms of attacks. The cyber security workforce, already suffering a skills crisis, may lack the soft skills required to effectively tackle these issues, many of which could be solved if the industry didn't rely so heavily on recruiting graduates and rather looked towards hiring apprentices, argues Phil Chapman of Firebrand Training.

negative: A simulation of a COVID-19 epidemic based on a deterministic SEIR model An epidemic disease caused by a new coronavirus has spread in Northern Italy with a strong contagion rate. We implement an SEIR model to compute the infected population and number of casualties of this epidemic. The example may ideally regard the situation in the Italian Region of Lombardy, where the epidemic started on February 25. We calibrate the model with the number of dead individuals to date (May 5, 2020) and constraint the parameters on the basis of values reported in the literature. The peak occurs at day 37 (March 31) approximately, when there is a rapid decrease, with a reproduction ratio R0 = 3 initially, 1.36 at day 22 and 0.8 after day 35, indicating different degrees of lockdown. The predicted death toll is approximately 15600 casualties, with 2.7 million infected individuals at the end of the epidemic. The incubation period providing a better fit of the dead individuals is 4.25 days and the infection period is 4 days, with a fatality rate of 0.00144/day [values based on the reported (official) number of casualties]. The infection fatality rate (IFR) is 0.57 %, and 2.36 % if twice the reported number of casualties is assumed. However, these rates depend on the initially exposed individuals. If approximately nine times more individuals are exposed, there are three times more infected people at the end of the epidemic and IFR = 0.47 %. If we relax these constraints and use a wider range of lower and upper bounds for the incubation and infection periods, we observe that a higher incubation period (13 versus 4.25 days) gives the same IFR (0.6 versus 0.57 %), but nine times more exposed individuals in the first case. Therefore, a precise determination of the fatality rate is subject to the knowledge of the characteristics of the epidemic.

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: On estimating the number of deaths related to Covid-19 In this paper, we discuss an explicit model function that can estimate the total number of deaths in the population, and particularly, estimate the cumulative number of deaths in the United States due to the current Covid-19 virus. We compare the modeling results to two related existing models based on a new criteria and several existing criteria for model selection. The results show the proposed model fits significantly better than the other two related models based on the U.S. Covid-19 death data. We observe that the errors of the fitted data and the predicted data points on the total number of deaths in the U.S. on the last available data point and the next coming day are less than 0.5% and 2.0%, respectively. The results show very encouraging predictability for the model. The new model predicts that the maximum total number of deaths will be approximately 62,100 across the United States due to the Covid-19 virus, and with a 95% confidence that the expected total death toll will be between 60,951 and 63,249 deaths based on the data until 22 April, 2020. If there is a significant change in the coming days due to various testing strategies, social-distancing policies, the reopening of community strategies, or a stay-home policy, the predicted death tolls will definitely change. Future work can be explored further to apply the proposed model to global Covid-19 death data and to other applications, including human population mortality, the spread of disease, and different topics such as movie reviews in recommender systems.

negative: Ghosts A travel barrier to tourism recovery Abstract This study aims to assess whether or not beliefs in ghosts really deter tourists from traveling to disaster-hit destinations. To many it may appear that cultural differences do play a role in travel decision making between Asian and Western tourists. However, it is vital to provide empirical evidence of the impact of cultural differences in beliefs through a case study of the tsunami-hit destinations. Thus, this study aims to examine tourist barriers associated with tsunami-hit destinations, and also to assess cultural differences regarding such beliefs between Asians tourists from China and Thailand and Western tourists from Britain, Germany, and the United States and also across demographic profile.

negative: MERS-CoV: Ein aktueller Überblick The following article gives a current overview of the newly emerging Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Since first time in summer 2012 in some countries in the Arabian Peninsula there were a number of severe infections of the respiratory tract caused by the new coronavirus. The majority of cases of illness were reported from Saudi Arabia, in Germany several imported cases of the disease have been reported. After beginning with flu-like-symptoms usually follows a pneumonia with a transition to an acute respiratory distress syndrome. The mortality rate is estimated at 55%. In the travel medical advice it should be elucidated about the disease and for that reason it is of great importance also for occupational medicine.

negative: Celebrating TB day at the time of COVID-19 March 24th, the tuberculosis (TB) day, is the global call to raise awareness, celebrate successes and remind the world that TB is still the N°1 killer among the infectious causes of death [1]. TB is preventable and curable disease, and its control is a highly cost-effective health intervention. However, diagnostic delay and inadequate treatment contribute to the severity and mortality of the disease as well as the risk of transmission and development of drug resistance. Despite the fact that TB disproportionately impacts low- and middle- income countries, it does not spare any country in the world including those in the European Union/European Economic Area where more than 4000 of people still die for the disease every year [2]. Moreover, the high number of multidrug-resistant (MDR)-TB cases in some countries of the World Health Organization (WHO) European Region poses a growing public health threat. Despite the sheer numbers, TB has for too long been overshadowed by HIV and malaria, and currently by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) epidemic.

negative: Scientific research progress of COVID‐19/SARS‐CoV‐2 in the first five months A cluster of pneumonia (COVID‐19) cases have been found in Wuhan China in late December, 2019, and subsequently, a novel coronavirus with a positive stranded RNA was identified to be the aetiological virus (severe acute respiratory syndrome coronavirus 2, SARS‐CoV‐2), which has a phylogenetic similarity to severe acute respiratory syndrome coronavirus (SARS‐CoV). SARS‐CoV‐2 transmits mainly through droplets and close contact and the elder or people with chronic diseases are high‐risk population. People affected by SARS‐CoV‐2 can be asymptomatic, which brings about more difficulties to control the transmission. COVID‐19 has become pandemic rapidly after onset, and so far the infected people have been above 2 000 000 and more than 130 000 died worldwide according to COVID‐19 situation dashboard of World Health Organization (https://covid19.who.int). Here, we summarized the current known knowledge regarding epidemiological, pathogenesis, pathology, clinical features, comorbidities and treatment of COVID‐19/ SARS‐CoV‐2 as reference for the prevention and control COVID‐19.

negative: What does and does not correlate with COVID-19 death rates We correlate county-level COVID-19 death rates with key variables using both linear regression and negative binomial mixed models, although we focus on linear regression models. We include four sets of variables: socio-economic variables, county-level health variables, modes of commuting, and climate and pollution patterns. Our analysis studies daily death rates from April 4, 2020 to May 27, 2020. We estimate correlation patterns both across states, as well as within states. For both models, we find higher shares of African American residents in the county are correlated with higher death rates. However, when we restrict ourselves to correlation patterns within a given state, the statistical significance of the correlation of death rates with the share of African Americans, while remaining positive, wanes. We find similar results for the share of elderly in the county. We find that higher amounts of commuting via public transportation, relative to telecommuting, is correlated with higher death rates. The correlation between driving into work, relative to telecommuting, and death rates is also positive across both models, but statistically significant only when we look across states and counties. We also find that a higher share of people not working, and thus not commuting either because they are elderly, children or unemployed, is correlated with higher death rates. Counties with higher home values, higher summer temperatures, and lower winter temperatures have higher death rates. Contrary to past work, we do not find a correlation between pollution and death rates. Also importantly, we do not find that death rates are correlated with obesity rates, ICU beds per capita, or poverty rates. Finally, our model that looks within states yields estimates of how a given state's death rate compares to other states after controlling for the variables included in our model; this may be interpreted as a measure of how states are doing relative to others. We find that death rates in the Northeast are substantially higher compared to other states, even when we control for the four sets of variables above. Death rates are also statistically significantly higher in Michigan, Louisiana, Iowa, Indiana, and Colorado. California's death rate is the lowest across all states.

negative: Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon OBJECTIVE: Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBoV in Gabon. Two first studies was conducted to determine the prevalence of respiratory and enteric viruses in children under 5 years old who visited health centers for influenza-like illness (ILI) or diarrhea in Gabon from March 2010 to June 2011. However, HBoV was not included in the screening. The aim of this retrospective study was to evaluate the prevalence and the HBoV genotype in children under 5 years old with ILI or diarrhea in Gabon. RESULTS: A total of 810 nasal swabs and 317 feces samples collected during the two first study were analyzed among which 32 (4.4%) and 7 (2.2%) were positive for HBoV respectively. While there were no significant differences in prevalence between age groups in children with ILI, all children with diarrhea were under 12 months of age. Moreover, 84.4 and 42.8% were diagnosed in co-infections with at least one other respiratory virus, or enteric viruses respectively. Finally, HBoV subtype 1 has been detected in both respiratory and gastrointestinal tracts with very low variability.

negative: Use of excess mortality associated with the COVID-19 epidemic as an epidemiological surveillance strategy - preliminary results of the evaluation of six Brazilian capitals In early 2020, the World Health Organization (WHO) recognized the pandemic situation of the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which causes Coronavirus Disease-2019 (COVID-19). In Brazil by the end of April 2020, another 110 thousand cases and 5,000 deaths had been confirmed. The scarcity of laboratory resources and overload of the care network, added to the broad clinical spectrum of the disease, can make it difficult to capture all mortality from this disease through epidemiological surveillance based on individual notification of cases. The aim of this study was to evaluate the excess of deaths in Brazilian capitals with the highest incidence of COVID-19, as a way of validating the method, we also evaluated a capital with low incidence. We assessed weekly mortality from all causes during the year 2020, up to the epidemiological week 17, compared with the previous year. The data were obtained through the National Civil Registry Information Center (CNIRC, acronym in Portuguese). We estimate the expected mortality and the 95% confidence interval by projecting the observed mortality in 2019 for the population of 2020. In the five capitals with the highest incidences it was possible to identify excess deaths in the pandemic period, the age group most affected were those over 60 years old, 31% of the excess deaths occurred in the population between 20 and 59 years old. There was a strong correlation (r = 0.94) between the excess of deaths in each city and the number of deaths confirmed by epidemiological surveillance. There was no excess of deaths in the capital with the lowest incidence, nor among the population under 20 years old. We estimate that epidemiological surveillance managed to capture only 52% of all mortality associated with the COVID-19 pandemic in the cities studied. Considering the simplicity of the method, its low cost and reliability for assessing the real burden of the disease, we believe that the assessment of excess mortality associated with the COVID-19 pandemic should be widely used as a complementary tool to regular epidemiological surveillance and its use should be encouraged by WHO.

negative: Letter to the Editor ”The Battle of Humans and COVID-19: A War without Smoke”

negative: Dynamics of COVID-19 outbreak in Poland: an epidemiological analysis of the first two months of the epidemic. INTRODUCTION Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus SARS-CoV-2. OBJECTIVES Our aim was to present an epidemiological analysis of the first two months (March and April 2020) of the COVID-19 epidemic in Poland. PATIENTS AND METHODS This analysis was based on data from epidemiological reports collected between March 4 and April 30, 2020, by the Chief Sanitary Inspectorate. These epidemiological reports include data on sociodemographic characteristics of new laboratory-confirmed COVID-19 cases, the number of COVID-19 related deaths, the number of recovered COVID-19 patients, as well as the number of laboratory tests performed. Results: From March 4 to April 30, 2020, a total of 12,877 laboratory-confirmed COVID-19 cases were registered in Poland (55.7% women, mean age 50.6 (20.5) years). The RT-PCR test was performed on 338,000 patients. The notification rate for COVID-19 was 33.2 per 100,000 inhabitants. One-third of laboratory-confirmed COVID-19 cases were among quarantined persons, 26.1% were related to the healthcare system (hospital or clinic), and 13.3% occurred in nursing homes. As of April 30, 2020, 644 COVID-19-related deaths were registered in Poland (46.5% women). The death rate for the whole country was 1.7 per 100,000 inhabitants. CONCLUSIONS Our data show higher notification rate for COVID-19 among women than men but men more likely to die from COVID-19. The notification rate for COVID-19 in Poland among women aged 45-54 years is two times higher than among men.

negative: SARS, MERS and COVID-19 among healthcare workers: A narrative review In the recent two decades, three global viral infectious diseases, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and coronavirus disease (COVID-19), have occurred worldwide. SARS occurred in November 2002, causing 8096 infected cases, as well as 774 deaths. MERS occurred in June, 2012, causing 2519 confirmed cases, along with 866 associated deaths. COVID-19 occurred in December 2019, as of 30 April 2020, a total of 3,024,059 clinical cases have been reported, including 208,112 deaths. Healthcare workers (HCWs) need to be in close contact with these virus-infected patients and their contaminated environments at work, thus leading to be infected in some of them, even a few of them are died in line of duty. In this review, we summarized the infection status of HCWs during the outbreak of SARS, MERS and COVID-19, with in-depth discussion, hoping to provoke sufficient attention to the HCWs infection status by more people.

negative: How Fear Appeal Approaches in COVID-19 Health Communication May Be Harming the Global Community. As health professionals develop health communication for coronavirus disease 2019 (COVID-19), we implore that these communication approaches do not include fear appeals. Fear appeals, also known as scare tactics, have been widely used to promote recommended preventive behaviors. We contend that unintended negative outcomes can result from fear appeals that intensify the already complex pandemic and efforts to contain it. We encourage public health professionals to reevaluate their desire to use fear appeals in COVID-19 health communication and recommend that evidence-based health communication be utilized to address the needs of a specific community, help people understand what they are being asked to do, explain step-by-step how to complete preventative behaviors, and consider external factors needed to support the uptake of behaviors. To aid health professionals in redirecting away from the use of fear appeals, we offer a phased approach to creating health communication messages during the COVID-19 crisis.

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: Modeling COVID-19: Forecasting and analyzing the dynamics of the outbreak in Hubei and Turkey As the pandemic of Coronavirus Disease 2019 (COVID-19) rages throughout the world, accurate modeling of the dynamics thereof is essential. However, since the availability and quality of data varies dramatically from region to region, accurate modeling directly from a global perspective is difficult, if not altogether impossible. Nevertheless, via local data collected by certain regions, it is possible to develop accurate local prediction tools, which may be coupled to develop global models. In this study, we analyze the dynamics of local outbreaks of COVID-19 via a coupled system of ordinary differential equations (ODEs). Utilizing the large amount of data available from the ebbing outbreak in Hubei, China as a testbed, we estimate the basic reproductive number, R0 of COVID-19 and predict the total cases, total deaths, and other features of the Hubei outbreak with a high level of accuracy. Through numerical experiments, we observe the effects of quarantine, social distancing, and COVID-19 testing on the dynamics of the outbreak. Using knowledge gleaned from the Hubei outbreak, we apply our model to analyze the dynamics of outbreak in Turkey. We provide forecasts for the peak of the outbreak and the total number of cases/deaths in Turkey, for varying levels of social distancing, quarantine, and COVID-19 testing.

negative: Assessing the risks of"infodemics"in response to COVID-19 epidemics Our society is built on a complex web of interdependencies whose effects become manifest during extraordinary events such as the COVID-19 pandemic, with shocks in one system propagating to the others to an exceptional extent. We analyzed more than 100 millions Twitter messages posted worldwide in 64 languages during the epidemic emergency due to SARS-CoV-2 and classified the reliability of news diffused. We found that waves of unreliable and low-quality information anticipate the epidemic ones, exposing entire countries to irrational social behavior and serious threats for public health. When the epidemics hit the same area, reliable information is quickly inoculated, like antibodies, and the system shifts focus towards certified informational sources. Contrary to mainstream beliefs, we show that human response to falsehood exhibits early-warning signals that might be mitigated with adequate communication strategies.

negative: Monitoring the Covid-19 epidemics in Italy from mortality data The mortality data can be used as an alternative source to monitor the status of Covid-19. We have studied a dataset including deaths up to the fourth week of April. There is a large excess, more pronounced at the beginning of the pandemic, showing a difference in age and gender compared to the Covid-19-confirmed cases. The study indicates that mortality information can be used to provide a less biased time profile of the pandemic.

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: Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in Fuyang, Anhui, China Abstract Objective To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China. Method In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People’s Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020. Results Of 125 patients infected SARS-CoV-2, the mean age was 38.76 years (SD, 13.799) and 71(56.8%) were male. Common symptoms include fever [116 (92.8%)], cough [102(81.6%)], and shortness of breath [57(45.6%)]. Lymphocytopenia developed in 48(38.4%) patients. 100(80.0%) patients showed bilateral pneumonia, 26(20.8%) patients showed multiple mottling and ground-glass opacity. All patients were given antiviral therapy. 19(15.2%) patients were transferred to the intensive care unit. By February 18, 47(37.6%) patients were discharged and none of patients died. Among the discharged patients, the median time of length of stay was 14.8 days (SD 4.16). Conclusion In this single-center, retrospective, descriptive study, fever is the most common symptom. Old age, chronic underlying diseases and smoking history may be risk factors to worse condition. Certain laboratory inspection may contribute to the judgment of the severity of illness.

negative: Prone Position in Management of COVID-19 Patients; a Commentary SARS-CoV-2 virus causes a pneumonia that was identified through fever, dyspnea, and acute respiratory symptoms and named COVID-19. This disease exacerbates in a number of patients and causes pulmonary edema, multi-organ failure, and acute respiratory distress syndrome (ARDS). Prevalence of ARDS among COVID-19 patients has been reported to be up to 17%. Among the introduced treatment methods for management of ARDS patients, prone position can be used as an adjuvant therapy for improving ventilation in these patients. Here we reviewed the literature regarding the role of prone position in management of COVID-19 patients.

negative: Self-assembling protein nanoparticles in the design of vaccines For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.

negative: Association of HLA class I with severe acute respiratory syndrome coronavirus infection BACKGROUND: The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. METHODS: HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. RESULTS: Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). CONCLUSIONS: Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.

negative: Diagnosing COVID-19: Did We Miss Anything? In late 2019, a mass of patients showing symptoms of a pneumonia-like disease of unknown origin emerged in Wuhan, China. Little did the world know it was the prelude of what would be a devastating pandemic. Samples were collected from these patients and the use of unbiased sequencing, and subsequent isolation of the pathogen using human airway epithelial cells led to the discovery of a novel coronavirus, named 2019-nCoV by the World Health Organization (WHO) and Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The disease caused by this virus is officially called the coronavirus disease 2019 (COVID-19).

negative: Afectación clínica y sintomatológica en pacientes mayores de 65 años por COVID-19

negative: Coronavirus latest: global infections pass 100,000.

negative: Fatal parvovirus B19 infections: a report of two autopsy cases Parvovirus B19 (PVB19) commonly infects children and is usually asymptomatic. Lethal outcomes of PVB19 infection are unusual; nevertheless, the two cases reported here are rare examples of PVB19-induced hemophagocytic syndrome and myocarditis in infants and children. The two cases show the indisputable usefulness of immunohistochemistry and in situ hybridization in the detection of PVB19. In the death investigations, histopathological examinations provided stronger evidence than did serology or molecular biology. The cases also highlight the importance of forensic autopsy in vaccine-related death. As vaccine-related deaths are what people fear and may cause declines in vaccination rates, it is important to clarify deaths temporally or causally associated with vaccine administration.

negative: Chapter 8 Transportation and _______ Abstract This chapter examines some topics that have not received as much attention, at least not concerning the potential roles for transportation in mitigating or avoiding public health impacts.

negative: Why do many pheasants released in the UK die, and how can we best reduce their natural mortality? Around 60% of pheasants released for shooting in the UK, an estimated 21 million birds, do not end up at their intended fate: being shot. This constitutes wastage, raising economic, environmental and ethical questions. We review what is known of the fates of released pheasants and consider why they do not directly contribute to the numbers harvested. We focus on four main explanations: predation, disease, starvation and dispersal, and highlight other important causes of mortality. For each explanation, we attempt to attribute levels of loss and identify timings or conditions when such losses may be heaviest. We review factors that exacerbate losses and methods available to mitigate them. Opportunities for amelioration may arise at all stages of the rearing and release of pheasants and involve changes to the conditions under which eggs are produced, the way young pheasants are reared or the management of the environment into which they are released. We found few studies investigating impacts of post-release management techniques on pheasant survival outside of the breeding season within a UK context. We found that a number of less commonly deployed practices focusing on early-life, pre-release management may improve survival. Given the scale of pheasant releasing in the UK, even improvements in survival of 1% would mean that ~ 350,000 fewer birds die of natural causes. Complementing current post-release management with proven novel pre-release management interventions could reduce the number of pheasants required for release, whilst maintaining current shooting levels. Lowering release numbers would lower financial costs, benefit the environment and reduce some ethical concerns over the release and shooting of reared pheasants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10344-018-1199-5) contains supplementary material, which is available to authorized users.

negative: The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen,Hubei,China Summary Background: Some articles have reported the epidemiological and clinical characteristics of coronavirus disease (COVID-19) in Wuhan, but other cities have rarely been reported. This study explored the epidemiology of COVID-19 in Jingmen. Methods: All confirmed cases of COVID-19 in the First People′s Hospital of Jingmen are included from January 12 to February 14,2020. Cases were analyzed for epidemiological data and were confirmed by real-time PCR. Findings: Of the 213 cases (108 men and 105 women) , 88 (41%) had exposure to Wuhan. The median age was 48 years ( range,2-88 years;IQR,35-58.5). Thirty-three severe patients with a median age of 66 years(range,33-82 years,IQR, 57-76) were treated in intensive care units; out of these patients, 66.7 %(22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the controlled measures, the number of new patients gradually decreased and nearly disappeared after 20 days. Interpretation: All people are susceptible to the COVID-19, but older males and those with comorbid conditions are more likely to have severe symptoms. Even though COVID-19 is highly contagious, control measures have proven to be very effective.

negative: Estimation of Tunisia COVID-19 infected cases based on mortality rate Estimating the number of people affected by COVID-19 is crucial in deciding which public health policies to follow. The authorities in different countries carry out mortality counts. We propose that the mortality reported in each country can be used to create an index of the number of actual cases at a given time. The specificity of whether or not deaths are rapid or not by COVID-19 also affects the number of actual cases. The number of days between the declaration of illness and death varies between 12 and 18 days. For a delay of 18 days, and using an estimated mortality rate of 2%, the number of cases in April 2020 in Tunisia would be 5 580 people. The pessimistic scenario predicts 22 320 infected people, and the most optimistic predicts 744 (which is the number of reported cases on April 12, 2020). Modeling the occurrence of COVID-19 cases is critical to assess the impact of policies to prevent the spread of the virus.

negative: Singapore claims first use of antibody test to track coronavirus infections ;Science ;AAAS In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19 The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely

negative: Short-Term Effects of Ambient Ozone, PM2.5, and Meteorological Factors on COVID-19 Confirmed Cases and Deaths in Queens, New York The outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been rapidly increasing in the United States. Boroughs of New York City, including Queens county, turn out to be the epicenters of this infection. According to the data provided by the New York State Department of Health, most of the cases of new COVID-19 infections in New York City have been found in the Queens county where 42,023 people have tested positive, and 3221 people have died as of 20 April 2020. Person-to-person transmission and travels were implicated in the initial spread of the outbreaks, but factors related to the late phase of rapidly spreading outbreaks in March and April are still uncertain. A few previous studies have explored the links between air pollution and COVID-19 infections, but more data is needed to understand the effects of short-term exposures of air pollutants and meteorological factors on the spread of COVID-19 infections, particularly in the U.S. disease epicenters. In this study, we have focused on ozone and PM2.5, two major air pollutants in New York City, which were previously found to be associated with respiratory viral infections. The aim of our regression modeling was to explore the associations among ozone, PM2.5, daily meteorological variables (wind speed, temperature, relative humidity, absolute humidity, cloud percentages, and precipitation levels), and COVID-19 confirmed new cases and new deaths in Queens county, New York during March and April 2020. The results from these analyses showed that daily average temperature, daily maximum eight-hour ozone concentration, average relative humidity, and cloud percentages were significantly and positively associated with new confirmed cases related to COVID-19; none of these variables showed significant associations with new deaths related to COVID-19. The findings indicate that short-term exposures to ozone and other meteorological factors can influence COVID-19 transmission and initiation of the disease, but disease aggravation and mortality depend on other factors.

negative: Effects of media reporting on mitigating spread of COVID-19 in the early phase of the outbreak The 2019 novel coronavirus disease (COVID-19) is running rampantly in China and is swiftly spreading to other countries in the world, which causes a great concern on the global public health. The absence of specific therapeutic treatment or effective vaccine against COVID-19 call for other avenues of the prevention and control measures. Media reporting is thought to be effective to curb the spreading of an emergency disease in the early stage. Cross-correlation analysis based on our collected data demonstrated a strong correlation between media data and the infection case data. Thus we proposed a deterministic dynamical model to examine the interaction of the disease progression and the media reports and to investigate the effectiveness of media reporting on mitigating the spread of COVID-19. The basic reproduction number was estimated as 5.3167 through parameterization of the model with the number of cumulative confirmed cases, the number of cumulative deaths and the daily number of media items. Sensitivity analysis suggested that, during the early phase of the COVID-19 outbreak, enhancing the response rate of the media reporting to the severity of COVID-19, and enhancing the response rate of the public awareness to the media reports, both can bring forward the peak time and reduce the peak size of the infection significantly. These findings suggested that besides improving the medical levels, media coverage can be considered as an effective way to mitigate the disease spreading during the initial stage of an outbreak.

negative: Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review BACKGROUND: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement. OBJECTIVE: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. METHODS: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease. RESULTS: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients. CONCLUSION: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.

negative: Inferring Timing of Infection Using Within-host SARS-CoV-2 Infection Dynamics Model: Are "Imported Cases" Truly Imported? Importance: Although the COVID-19 epidemic in some countries such as China are in the last phase by large effort for containment of the disease, another outbreaks can occur because huge susceptible population remains. Further, there remain countries in the early phase of outbreak with zero or limited number of cases in southern hemisphere countries. In those countries at risk of future outbreak, ascertaining whether cases are imported or the result of local secondary transmission is important for government to shape appropriate public health strategies. Objective: To develop a method to estimate timing of infection establishment, which helps differentiate imported and autochthonous cases. Design, Setting and Participants: Of the first 18 cases reported in Singapore, 12 were used in our study (1 case with insufficient data and 5 on anti-viral treatment were excluded from the analysis). The viral load data from these initial cases considered imported due to their travel history to Wuhan were analyzed. Another viral load data from 3 cases reported from Zhuhai, China, for whom exposed day were known, were also analyzed to determine the viral load threshold for infection establishment. Exposures: SARS-CoV-2 infection confirmed by the polymerase-chain-reaction (PCR) test. Main Outcomes and Measures: The timing of infection establishment of each case was assessed by analysing viral load data after symptom onset using a within-host viral dynamics model for SARS-CoV-2. Estimated timing of infection will indicate whether cases are imported or autochthonous transmission within Singapore. Results: Six among the 12 cases were clearly imported cases, whereas we could not rule out the possibility of secondary transmission for the rest of 6 cases, which collectively evidenced ongoing transmission in Singapore. For the 6 cases who could be the results of secondary transmission, further investigation to identify the source of infection within Singapore should be warranted (i.e., contact tracing). Conclusions and Relevance: In an early phase of outbreak due to entrance or re-entrance of the virus to countries/communities, collecting viral load data over time from cases from symptom onset is highly recommended, because viral load data are valuable to infer the timing of infection and distinguish between imported cases and ongoing local transmission.

negative: Implementation of an Emergency Use Authorization Test During an Impending National Crisis Abstract The laboratory response to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may be termed heroic. From the identification of the novel coronavirus to implementation of routine laboratory testing around the world to the development of potential vaccines, laboratories have played a critical role in the efforts to curtail this pandemic. In this brief report, we review our own effort at a mid-sized, rural, academic medical center to implement a molecular test for the virus; and, we share insights and lessons learned from that process which might be helpful in similar situations in the future.

negative: Working from home in the time of covid-19: how to best preserve occupational health?

negative: Identification and characterization of Coronaviridae genomes from Vietnamese bats and rats based on conserved protein domains The Coronaviridae family of viruses encompasses a group of pathogens with a zoonotic potential as observed from previous outbreaks of the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Accordingly, it seems important to identify and document the coronaviruses in animal reservoirs, many of which are uncharacterized and potentially missed by more standard diagnostic assays. A combination of sensitive deep sequencing technology and computational algorithms is essential for virus surveillance, especially for characterizing novel- or distantly related virus strains. Here, we explore the use of profile Hidden Markov Model-defined Pfam protein domains (Pfam domains) encoded by new sequences as a Coronaviridae sequence classification tool. The encoded domains are used first in a triage to identify potential Coronaviridae sequences and then processed using a Random Forest method to classify the sequences to the Coronaviridae genus level. The application of this algorithm on Coronaviridae genomes assembled from agnostic deep sequencing data from surveillance of bats and rats in Dong Thap province (Vietnam) identified thirty-four Alphacoronavirus and eleven Betacoronavirus genomes. This collection of bat and rat coronaviruses genomes provided essential information on the local diversity of coronaviruses and substantially expanded the number of coronavirus full genomes available from bat and rats and may facilitate further molecular studies on this group of viruses.

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: Dr. Wu Lien Teh, plague fighter and father of the Chinese public health system

negative: Estimation of Transmission Potential and Severity of COVID-19 in Romania and Pakistan During the outbreak of an epidemic, it is of immense interest to monitor the effects of containment measures and forecast of outbreak including epidemic peak. To confront the epidemic, a simple S I R model is used to simulate the number of affected patients of Coronavirus disease in Romania and Pakistan. The model captures the growth in case onsets and the estimated results are almost compatible with the actual reported cases. Through the calibration of parameters, forecast for the appearance of new cases in Romania and Pakistan is reported till the end of this year by analysing the current situation. The constant level of number of patients and time-to-reach this level is also reported through the simulations. The drastic condition is also discussed which may occur if all the preventive restraints are removed.

negative: CIRD-F: Spread and Influence of COVID-19 in China The outbreak of coronavirus disease 2019 (COVID-19) has been spreading rapidly in China and the Chinese government took a series of policies to control the epidemic. Therefore, it will be helpful to predict the tendency of the epidemic and analyze the influence of official policies. Existing models for prediction, such as cabin models and individual-based models, are either oversimplified or too meticulous, and the influence of the epidemic was studied much more than that of official policies. To predict the epidemic tendency, we consider four groups of people, and establish a propagation dynamics model. We also create a negative feedback to quantify the public vigilance to the epidemic. We evaluate the tendency of epidemic in Hubei and China except Hubei separately to predict the situation of the whole country. Experiments show that the epidemic will terminate around 17 March 2020 and the final number of cumulative infections will be about 78 191 (prediction interval, 74 872 to 82 474). By changing the parameters of the model accordingly, we demonstrate the control effect of the policies of the government on the epidemic situation, which can reduce about 68% possible infections. At the same time, we use the capital asset pricing model with dummy variable to evaluate the effects of the epidemic and official policies on the revenue of multiple industries.

negative: Conquest of COVID‐19. Publish it to Death? Some diseases can be cured by medical interventions, others not. When not, are there other approaches to control or cure? One possibility is to try to publish a disease to death, a therapy strategy first proposed by my late colleague Prof. David Golde from UCLA (see below). Here I consider whether this strategy is working in the fight against severe acute respiratory syndrome‐cornavirsu‐2 (SARS‐CoV‐2) pandemic and the associated coronavirus infectious disease‐2019 (COVID‐19).

negative: Novel coronavirus: how things are in Wuhan

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: Generic probabilistic modelling and non-homogeneity issues for the UK epidemic of COVID-19 Coronavirus COVID-19 spreads through the population mostly based on social contact. To gauge the potential for widespread contagion, to cope with associated uncertainty and to inform its mitigation, more accurate and robust modelling is centrally important for policy making. We provide a flexible modelling approach that increases the accuracy with which insights can be made. We use this to analyse different scenarios relevant to the COVID-19 situation in the UK. We present a stochastic model that captures the inherently probabilistic nature of contagion between population members. The computational nature of our model means that spatial constraints (e.g., communities and regions), the susceptibility of different age groups and other factors such as medical pre-histories can be incorporated with ease. We analyse different possible scenarios of the COVID-19 situation in the UK. Our model is robust to small changes in the parameters and is flexible in being able to deal with different scenarios. This approach goes beyond the convention of representing the spread of an epidemic through a fixed cycle of susceptibility, infection and recovery (SIR). It is important to emphasise that standard SIR-type models, unlike our model, are not flexible enough and are also not stochastic and hence should be used with extreme caution. Our model allows both heterogeneity and inherent uncertainty to be incorporated. Due to the scarcity of verified data, we draw insights by calibrating our model using parameters from other relevant sources, including agreement on average (mean field) with parameters in SIR-based models. We use the model to assess parameter sensitivity for a number of key variables that characterise the COVID-19 epidemic. We also test several control parameters with respect to their influence on the severity of the outbreak. Our analysis shows that due to inclusion of spatial heterogeneity in the population and the asynchronous timing of the epidemic across different areas, the severity of the epidemic might be lower than expected from other models. We find that one of the most crucial control parameters that may significantly reduce the severity of the epidemic is the degree of separation of vulnerable people and people aged 70 years and over, but note also that isolation of other groups has an effect on the severity of the epidemic. It is important to remember that models are there to advise and not to replace reality, and that any action should be coordinated and approved by public health experts with experience in dealing with epidemics. The computational approach makes it possible for further extensive scenario-based analysis to be undertaken. This and a comprehensive study of sensitivity of the model to different parameters defining COVID-19 and its development will be the subject of our forthcoming paper. In that paper, we shall also extend the model where we will consider different probabilistic scenarios for infected people with mild and severe cases.

negative: Coronavirus disease 2019 in children: Surprising findings in the midst of a global pandemic. Question Coronavirus disease 2019 (COVID-19) is affecting millions of people worldwide. It seems that it affects mostly adults older than 40 years of age, and the death rate is highest for older individuals in the population. What should I tell parents worried about their children contracting the coronavirus (SARS-CoV-2) causing COVID-19, and what symptoms should I look for to determine if there is a need to test for the virus?Answer The COVID-19 global pandemic affects all ages. Severe respiratory manifestations have been the mainstay of illness in adults, with what seems to be rapid deterioration necessitating mechanical ventilation. Only 5% of those tested and found to have COVID-19 have been younger than 19 years, possibly owing to limited testing, as the symptoms in children are usually mild. Symptoms in children include fever, dry cough, rhinorrhea, sore throat, and fatigue, and in 10% diarrhea or vomiting. Rarely dyspnea or hypoxemia were also described. Blood tests and imaging have been shown to be of little value in children and should only be ordered for those in whom you would normally order these investigations for viral-like illness. No specific therapy is available and supportive care with rest, fluids, and antipyretics for children is the recommended approach. Ibuprofen or acetaminophen for fever and pain can be given. Antiviral and immunomodulatory treatment is not recommended at this time for otherwise healthy children, and corticosteroids should also not be used. Children with immunocompromised states should be isolated and avoid contact with others.

negative: Coronavirus Optimization Algorithm: A bioinspired metaheuristic based on the COVID-19 propagation model A novel bioinspired metaheuristic is proposed in this work, simulating how the coronavirus spreads and infects healthy people. From an initial individual (the patient zero), the coronavirus infects new patients at known rates, creating new populations of infected people. Every individual can either die or infect and, afterwards, be sent to the recovered population. Relevant terms such as re-infection probability, super-spreading rate or traveling rate are introduced in the model in order to simulate as accurately as possible the coronavirus activity. The Coronavirus Optimization Algorithm has two major advantages compared to other similar strategies. First, the input parameters are already set according to the disease statistics, preventing researchers from initializing them with arbitrary values. Second, the approach has the ability of ending after several iterations, without setting this value either. Infected population initially grows at an exponential rate but after some iterations, when considering social isolation measures and the high number recovered and dead people, the number of infected people starts decreasing in subsequent iterations. Furthermore, a parallel multi-virus version is proposed in which several coronavirus strains evolve over time and explore wider search space areas in less iterations. Finally, the metaheuristic has been combined with deep learning models, in order to find optimal hyperparameters during the training phase. As application case, the problem of electricity load time series forecasting has been addressed, showing quite remarkable performance.

negative: SUDDEN NATURAL DEATH | Infectious Diseases

negative: Counting the cost of COVID-19 Coronavirus disease 2019 (COVID-19) is the name given by the World Health Organization (WHO) to the highly contagious and infectious disease caused by the Novel Corona Virus or SARS-CoV-2, which was first reported on 31 December 2019 in Wuhan city of the capital of China's Hubei province. Due to the rapid increase in the number of infections worldwide, the WHO in March 2020, declared COVID-19 as a pandemic. Historically, first coronavirus had surfaced in 1965 with symptoms of common cold. Since then five different strands of this virus have emerged, most lethal of them was the Severe Acute Respiratory Syndrome (SARS), which infected about eight thousand people, killing ten percent of them. The COVID-19 is not the most deadly pandemic world has ever witnessed as the Spanish influenza pandemic, during 1918–19, killed more than fifty million people. Indeed COVID-19 has turned out to be the most lethal of all coronaviruses as it has infected at least three million people killing more than two hundred thousands of them in the first 4 months of its spread. Many politicians and social scientists have dubbed the depression, being caused by COVID-19, worse than that caused by the Second World War. In this article, we shall analyze economic, social, cultural, educational and political impact of the COVID-19.

negative: Covid-19: death rate is 0.66% and increases with age, study estimates.

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: COVID-19: Dying is Bad--Losing Life is Worse Background: COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020. Methods: Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020. Results: COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US. Conclusion: Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states "Prediction is difficult, especially when dealing with the future." We suggest that while dying is bad, losing life is even worse.

negative: Rabies elimination research: juxtaposing optimism, pragmatism and realism More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a ‘One Health’ approach.

negative: Demographic science aids in understanding the spread and fatality rates of COVID-19 Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the COVID-19 pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider both the age composition of local and national contexts as well as the social connectedness of older and younger generations. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted nowcasting.

negative: Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter’s streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter’s search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic—and undoubtedly more.

negative: Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs. Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.

negative: For Brazil’s Indigenous communities, pandemic revives memories of earlier plagues To the older generation of the Paiter Surui, the COVID-19 pandemic looks familiar The Indigenous people who inhabit the border of the Brazilian states of Rondônia and Mato Grosso suffered hundreds of deaths from measles and other infectious diseases in the decades after they first made contact with non-Indigenous people in 1969 The survivors “already experienced what is happening in the world today with the coronavirus,” says Rubens Naraikoe Surui, a young Indigenous leader Now, as the number of coronavirus cases ramps up in Brazil, the Pater Surui and other Indigenous people worry that they could be hard hit So far, 16 members of such groups are known to have had COVID-19 infections, and three have died: a 15-year-old Yanomami boy, a 78-year-old Tikuna man, and a 44-year-old Kokama woman

negative: Age- and sex-specific total mortality impacts of the early weeks of the Covid-19 pandemic in England and Wales: Application of a Bayesian model ensemble to mortality statistics Background: The Covid-19 pandemic affects mortality directly through infection as well as through changes in the social, environmental and healthcare determinants of health. The impacts on mortality are likely to vary, in both magnitude and timing, by age and sex. Our aim was to estimate the total mortality impacts of the pandemic, by sex, age group and week. Methods: We developed an ensemble of 16 Bayesian models that probabilistically estimate the weekly number of deaths that would be expected had the Covid-19 pandemic not occurred. The models account for seasonality of death rates, medium-long-term trends in death rates, the impact of temperature on death rates, association of death rates in each week on those in preceding week(s), and the impact of bank holidays. We used data from January 2010 through mid-February 2020 (i.e., week starting 15th February 2020) to estimate the parameters of each model, which was then used to predict the number of deaths for subsequent weeks as estimates of death rates if the pandemic had not occurred. We subtracted these estimates from the actual reported number of deaths to measure the total mortality impact of the pandemic. Results: In the week that began on 21st March, the same week that a national lockdown was put in place, there was a >92% probability that there were more deaths in men and women aged [≥]45 years than would occur in the absence of the pandemic; the probability was 100% from the subsequent week. Taken over the entire period from mid-February to 8th May 2020, there were an estimated [~] 49,200 (44,700-53,300) or 43% (37-48) more deaths than would be expected had the pandemic not taken place. 22,900 (19,300-26,100) of these deaths were in females (40% (32-48) higher than if there had not been a pandemic), and 26,300 (23,800-28,700) in males (46% (40-52) higher). The largest number of excess deaths occurred among women aged >85 years (12,400; 9,300-15,300), followed by men aged >85 years (9,600; 7,800-11,300) and 75-84 years (9,000; 7,500-10,300). The cause of death assigned to the majority (37,295) of these excess deaths was Covid-19. There was nonetheless a >99.99% probability that there has been an increase in deaths assigned to other causes in those aged [≥]45 years. However, by the 8th of May, the all-cause excess mortality had become virtually equal to deaths assigned to Covid-19, and non-Covid excess deaths had diminished to close to zero, or possibly become negative, in all age-sex groups. Interpretation: The death toll of Covid-19 pandemic, in middle and older ages, is substantially larger than the number of deaths reported as a result of confirmed infection, and was visible in vital statistics when the national lockdown was put in place. When all-cause mortality is considered, the mortality impact of the pandemic on men and women is more similar than when comparing deaths assigned to Covid-19 as underlying cause of death.

negative: Commentary on two reports on animal models of COVID‐19

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: Epidemiology and Clinical Features of Coronavirus disease 2019 in Children Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.

negative: COVID-19 infection in Italian people with diabetes: Lessons learned for our future (an experience to be used)

negative: Recent apprise on coronavirus and its terrible insinuations Epidemically increased evidence reveals that the link between the 2019-nCoV and other similar strain of coronaviruses circulating in bats and specifically the Rhinopodous bat sub-species. These sub-species are ample and widely present in Southern China, Middle East Africa and Europe. Recent studies show that more than 500 CoV have been identified in bats in China. The Center for Diseases Control and Prevention and the World Health Organization maintains a website that is updated frequently with new cases of MERS-CoV infection. As per WHO Situation report 16th, 24,554 number of cases confirmed globally out of which 99.22% cases from china. A new coronavirus (2019-nCoV) is causing respiratory syndrome mostly in Hubei Province, China. Corona Virus spread over 24 countries including Japan, India, Korea, and other countries 2019-CoV infection vary from mild, moderate or severe illness; the later includes severe pneumonia, ARDS, sepsis and septic shock. There are two diagnostic tests for coronavirus infection i.e. molecular test and serology test. In this review article there are the various recent cases of the patients that are suffering from the corona virus, the outcome of these studies is that corona virus infection is an epidemic disease which affects Central Nervous System (CNS).

negative: Risks Risk is our daily work and often our obsession – as risk researchers we are working on research projects which are intended to increase our knowledge about all aspects of risks. Being a “risk researcher” means looking at things through a specific perspective – the perspective of what negative consequences a natural or man-made event, a technology, a decision could probably have on the world we live in. Our perspective is a socio-scientific one. This means, we are analyzing what consequences do risks have on the society and what can we do to decrease or prevent them. This includes the possible actions of a single consumer as well as strategies of whole governments to manage risks. How are risks perceived by people? What kinds of knowledge are needed to deal with different kinds of risks? Who should be involved, and when? What to do if conflicts evolve about how to handle risks? How to communicate risks? It is our job to answer questions like these. We are dealing with these questions in many different thematic areas: food safety, climate change, chemicals, nanotechnology, electromagnetic fields, etc. These risks pose very different problems and it seems difficult to find general strategies to deal with them.

negative: Schutz vor SARS-CoV-2: Wie viel Maske sollte es sein?: COVID-19-Pandemie Gesunde junge Leute mit FFP-Masken im Supermarkt, reaktivierte Nähmaschinen im Dienst der Pandemiebekämpfung, dubiose Händler, die Masken meistbietend verhökern: Das Thema Masken bewegt die Gemüter. Die Unsicherheit ist groß. Wen harte Evidenz interessiert, der bleibt am Ende etwas ratlos zurück. Trotzdem gibt es gut begründete Empfehlungen — vor allem für medizinisches Personal. In der Bevölkerung gilt: Wenn Maske, dann richtig.

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: SEIR and Regression Model based COVID-19 outbreak predictions in India COVID-19 pandemic has become a major threat to the country. Till date, well tested medication or antidote is not available to cure this disease. According to WHO reports, COVID-19 is a severe acute respiratory syndrome which is transmitted through respiratory droplets and contact routes. Analysis of this disease requires major attention by the Government to take necessary steps in reducing the effect of this global pandemic. In this study, outbreak of this disease has been analysed for India till 30th March 2020 and predictions have been made for the number of cases for the next 2 weeks. SEIR model and Regression model have been used for predictions based on the data collected from John Hopkins University repository in the time period of 30th January 2020 to 30th March 2020. The performance of the models was evaluated using RMSLE and achieved 1.52 for SEIR model and 1.75 for the regression model. The RMSLE error rate between SEIR model and Regression model was found to be 2.01. Also, the value of R0 which is the spread of the disease was calculated to be 2.02. Expected cases may rise between 5000-6000 in the next two weeks of time. This study will help the Government and doctors in preparing their plans for the next two weeks. Based on the predictions for short-term interval, these models can be tuned for forecasting in long-term intervals.

negative: Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot Abstract Background Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. Method We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. Results Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately 3 h of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. Conclusion Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.

negative: Viral Infections in Children with Community-Acquired Pneumonia Viral pathogens are commonly isolated from children with community-acquired pneumonia (CAP). Viruses like respiratory syncytial virus, human rhinovirus, human metapneumovirus, parainfluenza viruses, and influenza may act as sole pathogens or may predispose to bacterial pneumonia by a variety of mechanisms. New, emerging, or reemerging viral pathogens occasionally cause outbreaks of severe respiratory tract infection in children. The 2009–2010 H1N1 influenza virus pandemic resulted in increased rates of influenza-related hospitalizations and deaths in children. Rapid viral diagnostic tests based on antigen detection or nucleic acid amplification are increasingly available for clinical use and confirm the importance of viral infection in children hospitalized with CAP. Recently published guidelines for the management of CAP in children note that positive viral test results can modify clinical decision making in children with suspected pneumonia by allowing antibacterial therapy to be withheld in the absence of clinical, laboratory, or radiographic findings that suggest bacterial coinfection.

negative: CoViD--19: An Automatic, Semiparametric Estimation Method for the Population Infected in Italy To date, official data on the number of people infected with the SARS-CoV-2 , responsible for the CoViD19 , have been released by the Italian Government just on the basis of a non representative sample of population which tested positive for the swab. However a reliable estimation of the number of infected, including asymptomatic people, turns out to be crucial in the preparation of operational schemes and to estimate the future number of people, who will require, to different extents, medical attentions. In order to overcome the current data shortcoming, this paper proposes a bootstrap driven, estimation procedure for the number of people infected with the SARSCoV2. This method is designed to be robust, automatic and suitable to generate estimations at regional level. Obtained results show that, while official data at March the 12th report 12.839 cases in Italy, people infected wiyh the SARSCoV2 could be as high as 105.789.

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: Knowledge and Beliefs of General Public of India on COVID-19: A Web-based Cross-sectional Survey Context: Despite many awareness programs conducted by the governments and other agencies, there are certain false beliefs among the general public of India towards the transmission, prevention, and treatment of COVID-19. Aims: To assess the knowledge and beliefs of the general public of India on COVID-19. Materials and Methods: A web-based cross-sectional survey was conducted between 20th March and 15th April 2020. A 17-item questionnaire was developed, validated, and used for the study. The questionnaire was randomly distributed among the public using Google forms through social media networks. Descriptive analysis was performed to represent the study characteristics, Chi-square test for assessing the associations among the study variables, and logistic regression analysis for identifying the factors influencing the beliefs. Results: A total of 462 participants with a mean (SD) age of 30.66 (11.31) years were responded to the questionnaire. Study participants are having fairly good knowledge of the basic aspects of COVID-19. However, a considerable fraction of participants were having false beliefs towards the transmission of new coronavirus, and prevention & treatment of COVID-19. It was observed that the participants who were aged 31-60 years and >60 years, education level of intermediate or diploma and high school certificate, and occupation as the unskilled workers had more of false beliefs towards COVID-19 compared to their counterparts. Conclusion: Though the overall knowledge on COVID-19 was good enough among the general public of India, still there is a need for education to avoid false beliefs especially among the people who are elderly, having a low level of education, and non-professional workers.

negative: Case fatality rate of novel coronavirus disease 2019 in China Abstract Background: A pandemic of coronavirus disease 2019 (COVID-19) which have caused more than 80 thousand persons infected globally is still ongoing. This study aims to calculate its case fatality rate (CFR). Methods: The method, termed as converged CFR calculation, was based on the formula of dividing the number of known deaths by the number of confirmed cases T days before, where T was an average time period from case confirmation to death. It was found that supposing a T, if it was smaller (bigger) than the true T, calculated CFRs would gradually increase (decrease) to infinitely near the true T with time went on. According to the law, the true T value could be determined by trends of daily CFRs calculated with different assumed T values (left of true T is decreasing, right is increasing). Then the CFR could be calculated. Results: CFR of COVID-19 in China except Hubei Province was 0.8% to 0.9%. So far, the CFR had accurately predicted the death numbers more than 3 weeks. CFR in Hubei of China was 5.4% by which the calculated death number corresponded with the reported number for 2 weeks. Conclusion: The method could be used for CFR calculating while pandemics are still ongoing. Dynamic monitoring of the daily CFRs trends could help outbreak-controller to have a clear vision in the timeliness of the case confirmation.

negative: The Myriad Ways in Which COVID-19 Revealed Character

negative: Relevant Cytokines in the Management of Community-Acquired Pneumonia Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed.

negative: Personal protective equipment and Covid 19- a risk to healthcare staff?

negative: The Fight against the 2019-nCoV Outbreak: an Arduous March Has Just Begun

negative: Perceived vulnerability to COVID-19 infection from event attendance: Results from Louisiana, USA, two weeks preceding the national emergency declaration In response to the mounting threat of COVID-19, we added questions to an ongoing food preference study held at Louisiana State University from March 3-12 of 2020. We asked 356 participants: (1) In your opinion, how likely is it that the spread of COVID-19 (the coronavirus) will cause a public health crisis in the United States? (2) How concerned are you that you will contract COVID-19 by attending events on campus? Participants' estimates of an impending national health crisis increased significantly during the study's second week (March 9-12) while concern about personally contracting COVID-19 from attending campus events increased only marginally during the study's final days. We find those expressing a higher likelihood of an impending national crisis were more concerned about contracting COVID-19 by attending campus events, suggesting a possible transmission from perceptions of national-level events to perceived personal vulnerability via local exposure. However, about 30% of participants perceived that COVID-19 would likely cause a public health crisis yet did not express concern about contracting COVID-19 from event attendance. These participants were significantly more likely to be younger students who agreed to participate in response to recruitment using same-day flyer distribution. Women expressed a higher likelihood of an emerging national health crisis, although they were not more concerned than men that attending campus events would result in virus contraction. Other groups (e.g., white, students younger than 25, highest income group) displayed similar concern about a national-level crisis, yet were significantly less concerned about contracting COVID-19 from attending campus events than others. Also, participants randomly assigned to information emphasizing the national impacts of food waste expressed significantly greater concern of contracting COVID-19 by attending campus events. These results provide some initial insight about how people perceived national and personal risks in the early stages of the COVID-19 crisis in Louisiana.

negative: Convalescent plasma as a potential therapy for COVID-19

negative: ECG changes after rabbit coronavirus infection Abstract This study examines the electrocardiographic (ECG) changes following rabbit coronavirus (RbCV) infection. We have shown that infection with RbCV results in the development of myocarditis and congestive heart failure and that some survivors of RbCV infection go on to develop dilated cardiomyopathy in the chronic phase. Serial ECGs were recorded on 31 RbCV-infected rabbits. Measurements of heart rate; P-R interval; QRS duration; QTc interval; and P-, QRS-, and T-wave voltages were taken. The recordings were also examined for disturbances of conduction, rhythm, and repolarization. The acute and subacute phases were characterized by sinus tachycardia with depressed R- and T-wave voltages as well as disturbances of conduction, rhythm, and repolarization. In most animals in the chronic phase, the sinus rate returned to near-baseline values with resolution of the QRS voltage changes. The ECG changes observed during RbCV infection are similar to the spectrum of interval/segment abnormalities, rhythm disturbances, conduction defects, and myocardial pathology seen in human myocarditis, heart failure, and dilated cardiomyopathy. Because animals often died suddenly in the absence of severe clinical signs of congestive heart failure during the acute phase, RbCV infection may increase ventricular vulnerability, resulting in sudden cardiac death. RbCV infection may provide a rare opportunity to study sudden cardiac death in an animal model in which the ventricle is capable of supporting ventricular fibrillation, and invasive techniques monitoring cardiac function can be performed.

negative: ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy Background: As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has the highest rate of SARS-CoV-2 infection, the highest number of deaths, and the highest mortality rate among large countries. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of the peculiar severity of COVID-19 among Italians, by looking at expression levels and variants in ACE2 and TMPRSS2 genes, which are crucial for viral infection. Methods: Exome and SNP array data from a large Italian cohort representative of the country's population were used to compare the burden of rare variants and the frequency of polymorphisms with European and East Asian populations. Moreover, we looked into gene expression databases to check for sex-unbalanced expression. Results: While we found no significant evidence that ACE2 is associated with disease severity/sex bias in the Italian population, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, contributing to the observed epidemiological data among Italian patients. Conclusions: Our analysis suggests a role for TMPRSS2 variants and expression levels in modulating COVID-19 severity, a hypothesis that fosters a rapid experimental validation on large cohorts of patients with different clinical manifestations.

negative: Mathematical modeling of COVID-19 fatality trends: Death kinetics law versus infection-to-death delay rule The COVID-19 pandemic has world-widely motivated numerous attempts to properly adjust classical epidemiological models, namely those of the SEIR-type, to the spreading characteristics of the novel Corona virus. In this context, the fundamental structure of the differential equations making up the SEIR models has remained largely unaltered—presuming that COVID-19 may be just “another epidemic”. We here take an alternative approach, by investigating the relevance of one key ingredient of the SEIR models, namely the death kinetics law. The latter is compared to an alternative approach, which we call infection-to-death delay rule. For that purpose, we check how well these two mathematical formulations are able to represent the publicly available country-specific data on recorded fatalities, across a selection of 57 different nations. Thereby, we consider that the model-governing parameters—namely, the death transmission coefficient for the death kinetics model, as well as the apparent fatality-to-case fraction and the characteristic fatal illness period for the infection-to-death delay rule—are time-invariant. For 55 out of the 57 countries, the infection-to-death delay rule turns out to represent the actual situation significantly more precisely than the classical death kinetics rule. We regard this as an important step towards making SEIR-approaches more fit for the COVID-19 spreading prediction challenge.

negative: Deliberate release: Plague – A review Yersinia pestis is the causative agent of plague and is considered one of the most likely pathogens to be used as a bioweapon. In humans, plague is a severe clinical infection that can rapidly progress with a high mortality despite antibiotic therapy. Therefore, early treatment of Y. pestis infection is crucial. This review provides an overview of its clinical manifestations, diagnosis, treatment, prophylaxis, and protection requirements for the use of clinicians. We discuss the likelihood of a deliberate release of plague and the feasibility of obtaining, isolating, culturing, transporting and dispersing plague in the context of an attack aimed at a westernized country. The current threat status and the medical and public health responses are reviewed. We also provide a brief review of the potential prehospital treatment strategy and vaccination against Y. pestis. Further, we discuss the plausibility of antibiotic resistant plague bacterium, F1-negative Y. pestis, and also the possibility of a plague mimic along with potential strategies of defense against these. An extensive literature search on the MEDLINE, EMBASE, and Web of Science databases was conducted to collate papers relevant to plague and its deliberate release. Our review concluded that the deliberate release of plague is feasible but unlikely to occur, and that a robust public health response and early treatment would rapidly halt the transmission of plague in the population. Front-line clinicians should be aware of the potential of a deliberate release of plague and prepared to instigate early isolation of patients. Moreover, front-line clinicians should be weary of the possibility of suicide attackers and mindful of the early escalation to public health organizations.

negative: “It feels like I’m the dirtiest person in the world.” Exploring the experiences of healthcare providers who survived MERS-CoV in Saudi Arabia Abstract In summer 2015, a Saudi 1000-bed tertiary care hospital experienced a serious outbreak among patients of Middle Eastern Respiratory Syndrome (MERS); during which, some healthcare providers contracted the virus, but none died. The outbreak provoked not only fear and stress; but also professional, emotional, ethical, and social conflicts and tension among healthcare providers and patients alike. Therefore, this study aims to explore what healthcare providers, who survived coronavirus infection, have experienced as a MERS patient and how the infection affected their relationship with their colleagues. Semi-structured, face-to-face interviews were conducted individually with seven survivors (healthcare providers). Each interview lasted up to 90min, and the data were analyzed using the thematic analysis technique. Within the participants’ rich and illuminating experiences, four themes were identified: caring for others in the defining moments, perceived prejudice behaviours and stigmatization, lived moments of traumatic fear and despair, and denial and underestimation of the seriousness of the disease at the individual and organizational levels. Survivors still suffered as a result of their traumatic experiences, which might negatively influence their performance. As these survivors are vulnerable, it is their organization’s responsibility to provide a system that embraces HCPs during and after disastrous events.

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: 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: COVID-19 presenting as acute pancreatitis Abstract The ongoing pandemic of Coronavirus disease-2019 (COVID-19) has spread over 200 countries worldwide, affecting >2 million people and >120,000 deaths. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most common symptoms include cough, shortness of breath, and fever. However, gastrointestinal manifestations of COVID-19 are increasingly being recognized. Herein, we report a case of COVID-19 who presented with acute pancreatitis (AP) without any other risk factors.

negative: Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Disease 2019 (COVID-19) Outbreak in January 2020 in China BACKGROUND: From the end of December 2019, coronavirus disease 2019 (COVID-19) began to spread in central China. Social capital is a measure of social trust, belonging, and participation. This study aimed to investigate the effects of social capital on sleep quality and the mechanisms involved in people who self-isolated at home for 14 days in January 2020 during the COVID-19 epidemic in central China. METHODS: Individuals (n=170) who self-isolated at home for 14 days in central China, completed self-reported questionnaires on the third day of isolation. Individual social capital was assessed using the Personal Social Capital Scale 16 (PSCI-16) questionnaire. Anxiety was assessed using the Self-Rating Anxiety Scale (SAS) questionnaire, stress was assessed using the Stanford Acute Stress Reaction (SASR) questionnaire, and sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Path analysis was performed to evaluate the relationships between a dependent variable (social capital) and two or more independent variables, using Pearson’s correlation analysis and structural equation modeling (SEM). RESULTS: Low levels of social capital were associated with increased levels of anxiety and stress, but increased levels of social capital were positively associated with increased quality of sleep. Anxiety was associated with stress and reduced sleep quality, and the combination of anxiety and stress reduced the positive effects of social capital on sleep quality. CONCLUSION: During a period of individual self-isolation during the COVID-19 virus epidemic in central China, increased social capital improved sleep quality by reducing anxiety and stress.

negative: How Fear Appeal Approaches in COVID-19 Health Communication May Be Harming the Global Community As health professionals develop health communication for coronavirus disease 2019 (COVID-19), we implore that these communication approaches do not include fear appeals. Fear appeals, also known as scare tactics, have been widely used to promote recommended preventive behaviors. We contend that unintended negative outcomes can result from fear appeals that intensify the already complex pandemic and efforts to contain it. We encourage public health professionals to reevaluate their desire to use fear appeals in COVID-19 health communication and recommend that evidence-based health communication be utilized to address the needs of a specific community, help people understand what they are being asked to do, explain step-by-step how to complete preventative behaviors, and consider external factors needed to support the uptake of behaviors. To aid health professionals in redirecting away from the use of fear appeals, we offer a phased approach to creating health communication messages during the COVID-19 crisis.

negative: Hajj in the Time of COVID-19 Abstract The recent outbreak of the novel COVID-19 is posing a severe public health risk across the globe. The Kingdom of Saudi Arabia (KSA) is one of the greatest destinations of religious congregations of Muslims. One of the largest religious gatherings is the Hajj that is anticipated to produce serious challenges of mass level exposures and spread to every corner of the world. Therefore, it is highly recommended that the Ministry of Hajj and Umrah (KSA), must regularly analyze the prevailing situation of COVID-19, and involve the religious scholars to make appropriate decisions about Hajj 2020. Although the Saudi government has been continuously taking all possible measures to contain the pandemic, people's cooperation is crucial in the fight against COVID-19.

negative: An evidence-based framework for priority clinical research questions for COVID-19 BACKGROUND: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. METHODS: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. CONCLUSIONS: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.

negative: Geriatric Medicine in Italy in the Time of Covid-19

negative: CoronaVis: A Real-time COVID-19 Tweets Data Analyzer and Data Repository Due to the nature of the data and public interaction, twitter is becoming more and more useful to understand and model various events. The goal of CoronaVis is to use tweets as the information shared by the people to visualize topic modeling, study subjectivity, and to model the human emotions during the COVID-19 pandemic. The main objective is to explore the psychology and behavior of the societies at large which can assist in managing the economic and social crisis during the ongoing pandemic as well as the after-effects of it. The novel coronavirus (COVID-19) pandemic forced people to stay at home to reduce the spread of the virus by maintaining social distancing. However, social media is keeping people connected both locally and globally. People are sharing information (e.g. personal opinions, some facts, news, status, etc.) on social media platforms which can be helpful to understand the various public behavior such as emotions, sentiments, and mobility during the ongoing pandemic. In this work, we develop a live application to observe the tweets on COVID-19 generated from the USA. In this paper, we have generated various data analytics over a period of time to study the changes in topics, subjectivity, and human emotions. We also share a cleaned and processed dataset named CoronaVis Twitter dataset (focused on the United States) available to the research community at https://github.com/mykabir/COVID19. This will enable the community to find more useful insights and create different applications and models to fight with COVID-19 pandemic and future pandemics as well.

negative: Understanding COVID-19 spreading through simulation modeling and scenarios comparison: preliminary results. Since late 2019 the world is facing the rapid spreading of a novel viral disease (SARS-CoV-2) provoked by the coronavirus 2 infection (COVID-19), declared pandemic last 12 March 2020. As of 27 March 2020, there were more than 500,000 confirmed cases and 23,335 deaths worldwide. In those places with a rapid growth in numbers of sick people in need of hospitalization and intensive care, this demand has over-saturate the medical facilities and, in turn, rise the mortality rate. In the absence of a vaccine, classical epidemiological measures such as testing, quarantine and physical distancing are ways to reduce the growing speed of new infections. Thus, these measures should be a priority for all governments in order to minimize the morbidity and mortality associated to this disease. System dynamics is widely used in many fields of the biological sciences to study and explain changing systems. The system dynamics approach can help us understand the rapid spread of an infectious disease such as COVID-19 and also generate scenarios to test the effect of different control measures. The aim of this study is to provide an open model (using STELLA® from Iseesystems) that can be customized to any area/region and by any user, allowing them to evaluate the different behavior of the COVID-19 dynamics under different scenarios. Thus, our intention is not to generate a model to accurately predict the evolution of the disease nor to supplant others more robust -official and non-official- from governments and renowned institutions. We believe that scenarios comparison can be an effective tool to convince the society of the need of a colossal and unprecedented effort to reduce new infections and ultimately, fatalities.

negative: Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children

negative: Second waves, social distancing, and the spread of COVID-19 across America We recently described a dynamic causal model of a COVID-19 outbreak within a single region. Here, we combine several of these (epidemic) models to create a (pandemic) model of viral spread among regions. Our focus is on a second wave of new cases that may result from loss of immunity--and the exchange of people between regions--and how mortality rates can be ameliorated under different strategic responses. In particular, we consider hard or soft social distancing strategies predicated on national (Federal) or regional (State) estimates of the prevalence of infection in the population. The modelling is demonstrated using timeseries of new cases and deaths from the United States to estimate the parameters of a factorial (compartmental) epidemiological model of each State and, crucially, coupling between States. Using Bayesian model reduction, we identify the effective connectivity between States that best explains the initial phases of the outbreak in the United States. Using the ensuing posterior parameter estimates, we then evaluate the likely outcomes of different policies in terms of mortality, working days lost due to lockdown and demands upon critical care. The provisional results of this modelling suggest that social distancing and loss of immunity are the two key factors that underwrite a return to endemic equilibrium.

negative: What Should I Do? The aim of the study was to examine the conflicting duties of a practicing surgeon who is at high risk for morbidity and mortality from Covid-19 infection. Should he opt out of the care of these patients or does his duty to care override other considerations? Older adults and those with serious medical conditions are at much greater risk for severe disease and death from Covid-19 infection. As a practicing frontline surgeon in a high risk group, the hospital offered the author, and other health care providers at high risk, the option to opt out of the care Covid-19 suspected or infected patients before an anticipated surge. What should the surgeon and other health care providers do? This is a question many are asking and having to answer. In this article, the author describes how difficult the situation of having any choice at all was and then how difficult it was to arrive at a decision. The duty to care and its limits, as well as obligations to society, family, co-workers, and to self, are examined. The author considers how he and others can contribute in other ways to patients and providers. The author arrives at a morally permissible and a rational decision to opt out. Health care workers at high risk can contribute in other ways to patients and providers. It still may not feel right.

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: COVID-19, City Lockdown, and Air Pollution: Evidence from China The rapid spread of COVID-19 is a global public health challenge. To prevent the escalation of its transmission, China locked down one-third of its cities and strictly restricted human mobility and economic activities. Using timely and comprehensive air quality data in China, we show that these counter-COVID-19 measures led to remarkable improvement in air quality. Within weeks, the Air Quality Index and PM2.5 concentrations were brought down by 25%. The effects are larger in colder, richer, and more industrialized cities. We estimate that such improvement would avert 24,000 to 36,000 premature deaths from air pollution on a monthly basis.

negative: Covid-19: UK death toll overtakes Italy's to become worst in Europe.

negative: Facing the future—what lessons could we learn from Covid-19?

negative: Glycosaminoglycans and infection. Glycosaminoglycans (GAGs) are complex linear polysaccharides expressed in intracellular compartments, at the cell surface, and in the extracellular environment where they interact with various molecules to regulate many cellular processes implicated in health and disease. Subversion of GAGs is a pathogenic strategy shared by a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi. Pathogens use GAGs at virtually every major portals of entry to promote their attachment and invasion of host cells, movement from one cell to another, and to protect themselves from immune attack. Pathogens co-opt fundamental activities of GAGs to accomplish these tasks. This ingenious strategy to subvert essential activities of GAGs likely prevented host organisms from deleting or inactivating these mechanisms during their evolution. The goal of this review is to provide a mechanistic overview of our current understanding of how microbes subvert GAGs at major steps of pathogenesis, using select GAG-pathogen interactions as representative examples.

negative: Cognitive biases operating behind the rejection of government safety advisories during COVID19 Pandemic

negative: Why lockdown? Simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the novel coronavirus Half the world's population is already under lock-down and the remainder will have to follow if the ongoing novel coronavirus 2019 (COVID-19) virus pandemic is to be contained. Faced with such brutally difficult decisions, it is essential that as many people as possible understand (1) why lock-down interventions represent the only realistic way for individual countries to contain their national-level epidemics before they turn into public health catastrophes, (2) why these need to be implemented so early, so aggressively and for such extended periods, and (3) why international co-operation to conditionally re-open trade and travel between countries that have successfully eliminated local transmission represents the only way to contain the pandemic at global level. Here we present simplified arithmetic models of COVID-19 transmission, control and elimination in user-friendly Shiny and Excel formats that allow non-specialists to explore, query, critique and understand the containment decisions facing their country and the world at large. Based on parameter values representative of the United Republic of Tanzania, which is still early enough in its epidemic cycle and response to avert a national catastrophe, national containment and elimination with less than 10 deaths is predicted for highly rigorous lock down within 5 weeks of the first confirmed cases and maintained for 15 weeks. However, elimination may only be sustained if case importation from outside the country is comprehensively contained by isolating for three weeks all incoming travellers, except those from countries certified as COVID-free in the future. Any substantive relaxation of these assumptions, specifically shortening the lock-down period, less rigorous lock-down or imperfect importation containment, may facilitate epidemic re-initiation, resulting in over half a million deaths unless rigorously contained a second time. Removing contact tracing and isolation has minimal impact on successful containment trajectories because high incidence of similar mild symptoms caused by other common pathogens attenuates detection success of COVID-19 testing. Nevertheless, contact tracing is recommended as an invaluable epidemiological surveillance platform for monitoring and characterizing the epidemic, and for understanding the influence of interventions on transmission dynamics.

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: Dataset on the COVID-19 Pandemic Situation in Tunisia with application to SIR Model April 9, 2020 marks 100 days since first cases of the Coronavirus Disease 2019 in China. In this crucial day with 1 436 198 confirmed infected cases in the world (New confirmed infected cases 82 837) and 85 521 deaths (6286 New daily deaths), the Global Level of the Covid-19 pandemic is evaluated at very high according to the World Health Organization (WHO) situation report. For most people, COVID-19 infection will cause mild illness (fever and at least one sign/symptom of respiratory disease), however for more than 3.4% of people, it can be fatal. Older people and those with pre-existing medical conditions (such as cardiovascular disease, chronic respiratory disease or diabetes) are at risk for severe disease and mortality. The incubation period of the virus is estimated to be between 2 and 14 days but longer incubation are reported. Furthermore, Data published by world authorities shows that statistics are different for different geographical regions and depends on many social and environmental factors. The sad reality of the COVID-19 is that there are currently no medications or vaccines proven to be effective for the treatment or prevention of the disease. The pandemic spread is consequenctly followed by a worldwide panic. Facing this dramatic uncertain situation, implementing a country wide strategy for social distancing and a general logistic policy for critical and life-saving supplies is an urgency for governomental and sanitaire authorities. Several mathematical models have been proposed for developed countries to predict the epidemic spread. However these models can't be adapted to developing countries due to the major differences in geographic, societal, economic and political adopted strategies. Here, we propose the application of the well known SIR model to the case study of Tunisia where Data are collected from three official databases showing differences in reporting methods. The proposed data could be useful to predict the spread of COVID-2019 and design a more reliable model that can estimate the finale size of the spread and help in monitoring infection control.

negative: The importance of microbiological testing for establishing cause of death in 42 forensic autopsies Abstract Microorganisms have always been one of the great challenges of humankind, being responsible for both high morbidity and mortality throughout history. In a forensic setting microbiological information will always be difficult to interpret due to lack of antemortem information and changes in flora postmortem. With this study we aim to review the use of microbiological procedures at our forensic institute. In a retrospective study including 42 autopsies performed at our Institute, where microbiological test had been applied, analyses were made with regard to: type of microbiological tests performed, microorganisms found, histological findings, antemortem information, C-reactive protein measurement and cause of death. Fiftyone different microorganisms were found distributed among 37 cases, bacteria being the most abundant. Nineteen of the cases were classified as having a microbiological related cause of death. C-reactive protein levels were raised in 14 cases of the 19 cases, histological findings either supported or were a decisive factor for the classification of microbiologically related cause of death in 14 cases. As a multitude of abundant microorganisms are able to cause infection under the right circumstances, all findings should be compared to anamnestic antemortem information, before conclusions are drawn. A definite list of true pathogens is nearly impossible to compile.

negative: World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Abstract An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.

negative: What variables can better predict the number of infections and deaths worldwide by SARS-CoV-2? Variation through time Lack of knowledge is the main problem we face in the global Covid-19 pandemic. SARS-CoV-2 is a new virus of which there were no previous studies. Using data from 50 very different countries and by means of a regression analysis, we studied the degree to which a series of variables (health indicators, environmental parameters, economic and social indicators, general characteristics of the country) were able to predict the number of people infected and killed by Covid-19. We also studied how these variables were changing their ability to predict the number of infected and dead by covid-19 during a 3 months period (March, April, May). The number of deaths by Covid-19 can always be predicted with great accuracy from the number of infected, regardless of the characteristics of the country (which has better or worse health, greater or lesser wealth, regardless of its population structure, etc.). Epidemiological measures to prevent transmission, mainly travel and mobility restrictions, proved to be much more efficient than having large hospital and medical resources. Inbound tourism turned out to be the variable that best predicts the number of infected (and, consequently, the number of deaths) happening in the different countries. Electricity consumption and degree of air pollution of a country (CO2 emissions, nitrous oxide and methane) are also capable of predicting, with great precision, the number of infections and deaths from Covid-19 in that country. Characteristics such as the area and population of a country also can predict, although to a lesser extent, the number of infected and dead. In contrast, a series of variables, which in principle would seem to have a greater influence on the evolution of Covid-19 (hospital bed density, Physicians per 1000 people, Researches in R & D, urban population, etc.), turned out to have very little ability to predict both the number of infected and the number of deaths from Covid-19. All this may explain why the countries that opted for social withdrawal policies since the start of the pandemic outbreak obtained better results.

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: Energetics based epitope screening in SARS CoV-2 (COVID 19) spike glycoprotein by Immuno-informatic analysis aiming to a suitable vaccine development The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratopic binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. We screened here few pairs of spike protein epitopic regions and selected their energetic, IC50, MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.

negative: And now for something completely different: from 2019-nCoV and COVID-19 to 2020-nMan

negative: Coronavirus 229E-Related Pneumonia in Immunocompromised Patients Coronaviruses strains 229E and OC43 have been associated with various respiratory illnesses ranging from the self-resolving common cold to severe pneumonia. Although chronic underlying conditions are major determinants of severe respiratory virus infections, few data about coronavirus-related pneumonia in immunocompromised patients are available. Here we report 2 well-documented cases of pneumonia related to coronavirus 229E, each with a different clinical presentation. Diagnosis was made on the basis of viral culture and electron microscopy findings that exhibited typical crown-like particles and through amplification of the viral genome by reverse transcriptase—polymerase chain reaction. On the basis of this report, coronaviruses should be considered as potential causative microorganisms of pneumonia in immunocompromised patients.

negative: Environmental perspective of COVID-19 Abstract The outbreak of COVID-19 has caused concerns globally. On 30 January WHO has declared it as a global health emergency. The easy spread of this virus made people to wear a mask as precautionary route, use gloves and hand sanitizer on a daily basis that resulted in generation of a massive amount of medical wastes in the environment. Millions of people have been put on lockdown in order to reduce the transmission of the virus. This epidemic has also changed the people's life style; caused extensive job losses and threatened the sustenance of millions of people, as businesses have shut down to control the spread of virus. All over the world, flights have been canceled and transport systems have been closed. Overall, the economic activities have been stopped and stock markets dropped along with the falling carbon emission. However, the lock down of the COVID-19 pandemic caused the air quality in many cities across the globe to improve and drop in water pollutions in some parts of the world.

negative: Potential T-cell and B-cell Epitopes of 2019-nCoV As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data. The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.

negative: Herd immunity or suppression strategy to combat COVID-19 Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called "herd immunity" has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden.Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants).In the face of the lack of an antiviral treatment and the lack of a protective vaccine one must state Taiwan has made the best out of the pandemic situation whereas Sweden failed completely.

negative: China's fight against COVID-19: What we have done and what we should do next? Background: On 12 March, the World Health Organization Director-General declared that "the threat of a global pandemic has become a reality", and the disease caused by the novel coronavirus, known as COVID-19, has become a global concern. Chinese efforts in curbing the virus have widely been recognized. Even the WHO has lauded the efforts of the Chinese government and advised the world to learn from China in fighting the disease. Since the outbreak of COVID-19, to curb the spread of the epidemic, the Chinese government has implemented unprecedented prevention interventions at the nationwide level. Currently, the outbreak in Wuhan is changing in a positive direction and has been effectively controlled. However, it is not clear what these measures were and how these measures changed to curb the outbreak of COVID-19 quickly. This study explored the characteristics and identified that China's control strategies have changed the epidemiological curve of rapidly rising new confirmed cases of COVID-19. This study also seeks to expand the experiences and lessons from this outbreak. Methods: We collected public health interventions measures from Jan 20, 2020, to 5 March 2020, and data from COVID-19 daily newly confirmed cases and daily cumulates cases to compare the control effects and changing trends. We performed a retrospective description of these intervention strategies from three stages. Besides, from the perspective of public health, the experiences and lessons exposed by this outbreak were roughly summarized. Results: These non-pharmacology interventions measures adopted by the Chinese government by the instruction and spirit of President Xi Jinping were timely and efficient. Conclusions: The present study was conducted to comprehensively analyze from a social epidemiology context. The results confirmed that these radical interventions taken by the Chinese government were effective, ambitious, and agile. However, we must be aware that the epidemic situation in Wuhan is still challenging. Keywords: China; COVID-19; intervention measures; change features, lessons

negative: AI-Driven Tools for Coronavirus Outbreak: Need of Active Learning and Cross-Population Train/Test Models on Multitudinal/Multimodal Data The novel coronavirus (COVID-19) outbreak, which was identified in late 2019, requires special attention because of its future epidemics and possible global threats. Beside clinical procedures and treatments, since Artificial Intelligence (AI) promises a new paradigm for healthcare, several different AI tools that are built upon Machine Learning (ML) algorithms are employed for analyzing data and decision-making processes. This means that AI-driven tools help identify COVID-19 outbreaks as well as forecast their nature of spread across the globe. However, unlike other healthcare issues, for COVID-19, to detect COVID-19, AI-driven tools are expected to have active learning-based cross-population train/test models that employs multitudinal and multimodal data, which is the primary purpose of the paper.

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: Community and Socioeconomic Factors Associated with COVID-19 in the United States: Zip code level cross sectional analysis Background: Multiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths. Methods: In this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socio-economic factors including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed. Results: Overall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code increased the proportion of positive cases by 0.77%, 0.23%, 1.64%, 1.83% and 0.46% respectively (P<0.01) with only population density remaining significant in zip codes with greater than median number of cases. In zips with greater than median number of deaths, no community/socio-economic factor contributed significantly to death. Conclusion: This study gives early signals of gender, and racial inequalities while providing overwhelming evidence of how population density may contribute to an increase in the number of positive cases of COVID-19.

negative: Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses Host responses to infections represent an important pathogenicity determiner, and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.

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: Excess mortality and potential undercounting of COVID-19 deaths by demographic group in Ohio Background: There are significant gaps in our understanding of the mortality effects of COVID-19 due to evolving diagnosis criteria, shortages of testing supplies, and challenges faced by physicians in treating patients in crisis environments. Accurate information on the number of deaths caused by COVID-19, both population wide and for demographic subgroups, is vital for policy makers and health care providers. Methods: We performed a retrospective study of weekly data for Ohio, a large American state. To estimate expected mortality in 2020 we employed data from 2010 through 2019, adjusted for secular trends and seasonality. We estimated excess mortality as the number of observed deaths less the number of expected deaths. We conducted the analysis for the entire population and by gender, race, age, and county of residence. Findings: We estimated 1,485 (95% CI 680-2,345) excess all-cause deaths in Ohio from March 15, 2020 through May 23, 2020. When limited to deaths due to natural causes, the estimated excess number of deaths increased to 2,504 (95% CI 1,633-3,221), reflecting the countervailing effect of a decrease in deaths due to external causes. While the largest number excess of deaths was observed in the 80+ age group, excess deaths comprised 45.3% (95% CI 21.8-60.9) of observed deaths in the groups corresponding to ages between 20 and 49 years old. Our estimate of 729 (95% CI 355-966) excess deaths for this group substantially exceeds the reported number of COVID-19 deaths of 51. We found elevated excess deaths for older individuals, blacks, and males. Interpretation: Our methodology addressed some of the challenges of estimating the number of deaths caused by COVID-19. Our finding of high proportional levels of excess deaths among younger age groups suggests that increases in the infection rates for this cohort may have a greater mortality impact than expected. Funding: None.

negative: Genome Organization of Canada Goose Coronavirus, A Novel Species Identified in a Mass Die-off of Canada Geese The complete genome of a novel coronavirus was sequenced directly from the cloacal swab of a Canada goose that perished in a die-off of Canada and Snow geese in Cambridge Bay, Nunavut, Canada. Comparative genomics and phylogenetic analysis indicate it is a new species of Gammacoronavirus, as it falls below the threshold of 90% amino acid similarity in the protein domains used to demarcate Coronaviridae. Additional features that distinguish the genome of Canada goose coronavirus include 6 novel ORFs, a partial duplication of the 4 gene and a presumptive change in the proteolytic processing of polyproteins 1a and 1ab.

negative: Reovirus Activates a Caspase-Independent Cell Death Pathway Virus-induced apoptosis is thought to be the primary mechanism of cell death following reovirus infection. Induction of cell death following reovirus infection is initiated by the incoming viral capsid proteins during cell entry and occurs via NF-κB-dependent activation of classical apoptotic pathways. Prototype reovirus strain T3D displays a higher cell-killing potential than strain T1L. To investigate how signaling pathways initiated by T3D and T1L differ, we methodically analyzed cell death pathways activated by these two viruses in L929 cells. We found that T3D activates NF-κB, initiator caspases, and effector caspases to a significantly greater extent than T1L. Surprisingly, blockade of NF-κB or caspases did not affect T3D-induced cell death. Cell death following T3D infection resulted in a reduction in cellular ATP levels and was sensitive to inhibition of the kinase activity of receptor interacting protein 1 (RIP1). Furthermore, membranes of T3D-infected cells were compromised. Based on the dispensability of caspases, a requirement for RIP1 kinase function, and the physiological status of infected cells, we conclude that reovirus can also induce an alternate, necrotic form of cell death described as necroptosis. We also found that induction of necroptosis requires synthesis of viral RNA or proteins, a step distinct from that necessary for the induction of apoptosis. Thus, our studies reveal that two different events in the reovirus replication cycle can injure host cells by distinct mechanisms.

negative: Fractal kinetics of COVID-19 pandemic We give an update to the original paper posted on 2/17/20 -- now (as of 3/1/20) the China deaths are rapidly decreasing, and we find an exponential decline to the power law similar to the that predicted by the network model of \citet{vazquez_polynomial_2006}. At the same time, we see non-China deaths increasing rapidly, and similar to the early behavior of the China statistics. Thus, we see three stages of the spread of the disease in terms of number of deaths: exponential growth, power-law behavior, and then exponential decline in the daily rate. (Original abstract) The novel coronavirus (COVID-19) continues to grow rapidly in China and is spreading in other parts of the world. The classic epidemiological approach in studying this growth is to quantify a reproduction number and infection time, and this is the approach followed by many studies on the epidemiology of this disease. However, this assumption leads to exponential growth, and while the growth rate is high, it is not following exponential behavior. One approach that is being used is to simply keep adjusting the reproduction number to match the dynamics. Other approaches use rate equations such as the SEIR and logistical models. Here we show that the current growth closely follows power-law kinetics, indicative of an underlying fractal or small-world network of connections between susceptible and infected individuals. Positive deviations from this growth law might indicate either a failure of the current containment efforts while negative deviations might indicate the beginnings of the end of the pandemic. We cannot predict the ultimate extent of the pandemic but can get an estimate of the growth of the disease.

negative: Polymers in the Delivery of siRNA for the Treatment of Virus Infections Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a “magic bullet”, due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by non-specific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data.

negative: Indications for healthcare surge capacity in European countries facing an exponential increase in COVID19 cases European healthcare systems face extreme pressure from COVID-19. We estimate such pressure by relating both country-specific accumulated COVID-19 deaths (intensity-approach) and active COVID-19 cases (magnitude-approach) to measures of healthcare system capacity: hospital beds, healthcare workers and healthcare expenditure. On March 25, 2020 - relative to Italy on March 11- we found Spain, The Netherlands and France to experience the highest pressure using the intensity-approach with a composite measure for healthcare capacity. For updates see www.covid-hcpressure.org

negative: Mutations, Recombination and Insertion in the Evolution of 2019-nCoV The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

negative: 1 Inleiding In augustus 2011 wijdde de Journal of the American Medical Association (JAMA) een redactioneel commentaar aan het groeiende probleem van morbide obese kinderen: kinderen die aan een dusdanig ernstige obesitas lijden dat hun gezondheid er direct door wordt bedreigd. In toenemende mate wordt bij deze kinderen zogenoemde bariatrische chirurgie toegepast, waarbij een maagband of een maagbypass wordt aangebracht om de voedselopname te verminderen. In het redactionele commentaar werd de vraag opgeworpen of voor deze kinderen niet een alternatieve benadering moet worden overwogen, namelijk het uit de ouderlijke macht ontzetten van hun ouders. In de Verenigde Staten is dit al een aantal malen daadwerkelijk gebeurd, zoals bij het 4 jaar oude en 138 pond wegende meisje Cory Andis.

negative: Coronavirus disease 2019 (COVID-19) pandemic and pregnancy The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2–2.5, indicating that 2–3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal−fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.

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: The value of early transmission dynamic studies in emerging infectious diseases

negative: Hazards There are many known hazards, including natural, man-made, and intentional. The source of risk is the wide range of hazards that are faced in almost every facet of life. The global society must contend with an array of hazards that may seem limitless, but which is actually limited owing to an individual’s genetics, spatial movements, habits, activities, and geographic locations. Physical location is the primary factor dictating what natural hazards a nation faces. Economic, industrial, and sociopolitical factors dictate hazards of technological and intentional origin. Moreover, with globalization, the speed and ease of international travel, and the emergence of global climate change patterns, every nation is connected to every other nation on the planet. This chapter begins with a short description of the disaster management processes of hazard identification and hazard analysis. Following this is a listing and descriptions of many of the hazards that possess catastrophic potential—in other words, those hazards that are capable of causing a disaster. Awareness of the hazards that affect a nation or region and full understanding of the causes and consequences of that hazard “portfolio” are the first steps in the disaster reduction process known as disaster risk management.

negative: 47 The Aircraft Cabin Environment Abstract Travel by air is a safe means of transport, but from the physiologic point of view it is a means of putting people at risk as well as a potential means of spreading infectious disease. Atmospheric pressure falls with altitude and above about 10,000 feet, blood desaturation leads to hypoxia. The aircraft cabin is pressurized to maintain an effective altitude below 8000 feet, which provides adequate protection for healthy travelers. Those individuals with cardiopulmonary impairment or other conditions affecting fitness to travel should seek advice from the airline in consultation with their medical provider. People are the primary source of microorganisms in aircraft cabins and are the most important reservoirs of infectious agents on aircraft. Recirculated cabin air is filtered to remove microorganisms, but this does not prevent person-to-person spread of infectious disease in vulnerable people. The World Health Organization and Centers for Disease Control and Prevention produce guidelines; and people with febrile illnesses should postpone air travel.

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: The Rapid Assessment and Early Warning Models for COVID-19 Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. Rapid assessment and early warning are essential for outbreak analysis in response to serious public health events. This paper reviews the current model analysis methods and conclusions from both micro and macro perspectives. The establishment of a comprehensive assessment model, and the use of model analysis prediction, is very efficient for the early warning of infectious diseases. This would significantly improve global surveillance capacity, particularly in developing regions, and improve basic training in infectious diseases and molecular epidemiology.

negative: The double burden of disease of COVID-19 in cardiovascular patients: overlapping conditions could lead to overlapping treatments

negative: Propagation analysis and prediction of the COVID-19 Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.

negative: Clinical observation and management of COVID-19 patients Three leading infectious disease experts in China were invited to share their bedside observations in the management of COVID-19 patients. Professor Taisheng Li was sent to Wuhan to provide frontline medical care. He depicts the clinical course of SARS-CoV-2 infection. Furthermore, he observes the significant abnormality of coagulation function and proposes that the early intravenous immunoglobulin and low molecular weight heparin anticoagulation therapy are very important. Professor Hongzhou Lu, a leader in China to try various anti-viral drugs, expresses concern on the quality of the ongoing clinical trials as most trials are small in scale and repetitive in nature, and emphasizes the importance of the quick publication of clinical trial results. Regarding the traditional Chinese medicine, Professor Lu suggests to develop a creative evaluation system because of the complicated chemical compositions. Professor Wenhong Zhang is responsible for Shanghai's overall clinical management of the COVID-19 cases. He introduces the team approach to manage COVID-19 patients. For severe or critically ill patients, in addition to the respiratory supportive treatment, timely multiorgan evaluation and treatment is very crucial. The medical decisions and interventions are carefully tailored to the unique characteristics of each patient.

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: Implications of COVID-19 for patients with pre-existing digestive diseases

negative: Psychological influence of Coronovirus disease 2019 (COVID-19) pandemic on the general public, medical workers and patients with mental disorders and its countermeasures Coronovirus disease 2019 (COVID-19) first broke out in Wuhan, Hubei Province, China in 2019, and now it spreads in more than 100 countries around the world. On January 30th, the World Health Organization (WHO) declared COVID-19 a public health emergency (PHEIC) of international concern. It was classified as a pandemic by (WHO) of the World Health Organization on March 11, 2020. With the increase in the number of cases reported by various countries every day, the COVID-19 pandemic has attracted more and more attention around the world. At the same time, this public health emergency has caused a variety of psychological problems, such as panic disorder, anxiety and depression. In addition, the Wuhan Mental Health Center's analysis of 2144 calls from the psychological hotline from February 4 to February 20, 2020 showed that general public accounted for 70%, medical workers accounted for 2.2%, patients with mental disorders accounted for 19.5%, and other personnel accounted for 8.3% (https://mp.weixin.qq.com/s/kmff1vnaLsT2d9xQkK5pwg). Therefore, while controlling the pandemic, the government should also pay attention to the mental health of the general public, medical workers and patients with mental disorders. Community mental health service system, online mental health service, telemedicine and other measures for patients with mental disorders may play a vital role during the pandemic.

negative: Knowledge and Awareness-based Survey of COVID-19 within the Eye Care Profession in Nepal: Misinformation is Hiding the Truth. Abstract Background: Nepal is currently under lockdown due to the COVID-19 pandemic with misinformation circulating on social media. This study aimed to analyse the knowledge and awareness of COVID-19 amongst eye care professionals in Nepal. Methodology: We invited 600 participants from 12 ophthalmic centres across Nepal to complete a qualitative, anonymous online survey. Results: Of the 600 eye care professionals invited, 310 (51%) participated in the survey. The symptoms of COVID-19 were known to 94%, whilst only 49% were aware of disease transmission. 98% of participants recognised the World Health Organization (WHO) awareness message, yet 41% of participants felt that consumption of hot drinks helps to destroy the virus. 41% disagreed that PPE should be mandatory for eye care practitioners. Conclusion: There is still considerable scope to improve the knowledge of COVID-19 amongst ophthalmic professionals in Nepal. Opinion is also split on measures to prevent transmission, with misinformation potentially fuelling confusion.

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: 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: The impact of traffic isolation in Wuhan on the spread of 2019-nCov The 2019-nCoV outbreak occurred near the Chinese Spring Festival transport period in Wuhan. As an important transportation center, the migration of Wuhan accelerated the spread of 2019-nCoV across mainland China. Based on the cumulative Baidu migration index (CBMI), we first analyzed the proportion of Wuhan's migrant population to other cities. Our results confirm that there is a significant correlation between the export population of Wuhan and reported cases in various regions. We subsequently found that the mortality rate in Hubei Province was much higher than that in other regions of mainland China, while the investigation of potential cases in Wuhan was far behind other provinces in Mainland China, which indicates the effectiveness of early isolation.

negative: National Early Warning Scores (NEWS / NEWS2) and COVID-19 deaths in care homes: a longitudinal ecological study Objectives:To investigate whether patterns of National Early Warning Scores (NEWS/NEWS2) in care homes during the COVID pandemic correspond with area-level COVID-19 death registrations from care homes. Study design: Longitudinal ecological study. Setting: 460 Care home units using the same software package to collect data on residents, from 46 local authority areas in England. Participants: 6,464 care home residents with at least one NEWS recording. Exposure measure: 29,656 anonymised person-level NEWS from 29/12/2019 to 20/05/2020 with component physiological measures: systolic blood pressure, respiratory rate, pulse rate, temperature, and oxygen saturation. Baseline values for each measure calculated using 80th and 20th centile scores before March 2020. Outcome measure: Time series comparison with Office for National Statistics (ONS) weekly reported registered deaths of care home residents where COVID-19 was the underlying cause of death, and all other deaths (excluding COVID-19) up to 10/05/2020. Results: Deaths due to COVID-19 were registered from 23/03/2020 in the study geographical areas. Between 23/03/2020 and 10/05/2020, there were 5,753 deaths (1,532 involving COVID-19 and 4,221 other causes). The proportion of above-baseline NEWS increased from 16/03/2020 and closely followed the rise and fall in COVID-19 deaths over the study period. The proportion of above-baseline oxygen saturation, respiratory rate and temperature measurements also increased approximately two weeks before peaks in care home deaths in corresponding geographical areas. Conclusions: NEWS may make a useful contribution to disease surveillance in care homes during the COVID-19 pandemic. Oxygen saturation, respiratory rate and temperature could be prioritised as they appear to signal rise in mortality almost as well as total NEWS. This study reinforces the need to collate data from care homes, to monitor and protect residents' health. Further work using individual level outcome data is needed to evaluate the role of NEWS in the early detection of resident illness.

negative: Use of an Automated Nested Multiplex Respiratory Pathogen PCR Panel Postmortem in the Pediatric Forensic Setting Respiratory pathogens have been detected in forensic investigations using multiple techniques; however, no study has examined the use of automated, nested, multiplex polymerase chain reaction (ANM‐PCR), commonly used in living patients, in the forensic setting. This retrospective study assessed the utility of ANM‐PCR in detecting respiratory pathogens in the pediatric forensic setting. Respiratory samples from 35 cases were tested for up to 20 respiratory pathogens. 51.4% of these cases yielded a positive ANM‐PCR result, 20% of which were considered the cause of or contributory to death. The most commonly detected pathogens were rhinovirus/enterovirus and respiratory syncytial virus, and these were the only pathogens determined to play a significant role in cause of death. The sampled sites and postmortem intervals tested did not affect the likelihood of a positive or negative test. ANM‐PCR panels are effective, affordable, and rapid ancillary tools in evaluating cause of death in the forensic pediatric population.

negative: The COVID-19 Pandemic: A Month of Bioethics in Finland Finland’s first COVID-19 infection was recorded in late January 2020. The person infected was a tourist from China in Lapland. Authorities recommended regular handwashing, coughing in one’s sleeve, not touching your face, physical distancing, and home lockdown for those at risk. The pandemic spread at different paces in different regions, and the first Finnish fatality was recorded on March 20 in Uusimaa province, where the number of documented infections was considerably higher than elsewhere. In late March, the parliament granted the government emergency powers for swift regulations and restrictions. Uusimaa province was isolated from the rest of the country for a fortnight, restaurants were closed, meetings of more than 10 people were forbidden, and schools and universities assumed distant-working modes, as did businesses and civil services where this was feasible.

negative: A patient reported outcome platform, a useful tool to improve monitoring and effective management of Covid-19–positive patients with cancer

negative: Scientific research progress of COVID-19/SARS-CoV-2 in the first five months A cluster of pneumonia (COVID-19) cases have been found in Wuhan China in late December, 2019, and subsequently, a novel coronavirus with a positive stranded RNA was identified to be the aetiological virus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which has a phylogenetic similarity to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV-2 transmits mainly through droplets and close contact and the elder or people with chronic diseases are high-risk population. People affected by SARS-CoV-2 can be asymptomatic, which brings about more difficulties to control the transmission. COVID-19 has become pandemic rapidly after onset, and so far the infected people have been above 2 000 000 and more than 130 000 died worldwide according to COVID-19 situation dashboard of World Health Organization (https://covid19.who.int). Here, we summarized the current known knowledge regarding epidemiological, pathogenesis, pathology, clinical features, comorbidities and treatment of COVID-19/ SARS-CoV-2 as reference for the prevention and control COVID-19.

negative: First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

negative: Rapid and accurate identification of COVID-19 infection through machine learning based on clinical available blood test results Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/.

negative: The fight against COVID-19: a report from the Italian trenches

negative: Estimating the burden of SARS-CoV-2 in France France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those <20 years of age (ya) to 10.1% in those >80ya. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project 2.8 million (range: 1.8–4.7) people, or 4.4% (range: 2.8–7.2) of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.

negative: The anti-HIV Drug Nelfinavir Mesylate (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections Coronaviruses belong to a group of enveloped, positive-single stranded RNA viruses that are known to cause severe respiratory distress in animals and humans. The current SARS coronavirus-2 (SARS CoV-2) pandemic has caused more than 2,000,000 infections globally and nearly 200,000 deaths. Coronaviruses enter susceptible cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after endocytosis of the virus into endosomes. Previous results with SARS and MERS CoV have shown that the Spike (S) glycoprotein is a major determinant of virus infectivity and immunogenicity. Herein, we show that expression of SARS CoV-2 S (S-n) glycoprotein after transient transfection of African green monkey kidney (Vero) cells caused extensive cell fusion in comparison to limited cell fusion caused by the SARS S (S-o) glycoprotein. S-n expression was detected intracellularly and on transfected Vero cell surfaces and caused the formation of very large multinucleated cells (syncytia) by 48 hours post transfection. These results are in agreement with published pathology observations of extensive syncytial formation in lung tissues of COVID-19 patients. This differential S-n versus S-o-mediated cell fusion suggests that SARS-CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular spaces and neutralizing antibodies. A systematic screening of several drugs for ability to inhibit S-n and S-o cell fusion revealed that the FDA approved HIV-protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n and S-o-mediated cell fusion in a dose-dependent manner. Complete inhibition of cell fusion was observed at a 10 micromolar concentration. Computational modeling and in silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n and S-o-mediated membrane fusion. Also, it is possible that nelfinavir mesylate acts on cellular processes to inhibit S proteolytic processing. These results warrant further investigations of the potential of nelfinavir mesylate as an antiviral drug, especially at early times after SARS-CoV-2 symptoms appear.

negative: El SARS-CoV-2, una nueva zoonosis pandémica que amenaza al mundo On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.

negative: The values of coagulation function in COVID-19 patients Objective: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. Methods: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), 2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). Result: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. Conclusion: The coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.

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: Grief and the COVID-19 Pandemic in Older Adults In few periods in human history have bereavement and grief been on so many people's minds as they are today. As the coronavirus disease 2019 (COVID-19) ravages the world, we have seen many perish in a short time. Many have died alone because of requirements for physical distancing. Even more will succumb as COVID-19 continues to spread. Moreover, deaths from other causes, numbering over 50 million annually, are also happening amid physical distancing and other COVID-19-related challenges. The pandemic is affecting the way terminally ill patients are being cared for, when and how people are dying of other causes, and how bodies are being handled and bereavement rituals performed. The bereaved are required to grieve without the support of usual social and cultural rituals. Grieving is further encumbered by cascading life stressors deriving from policies needed to mitigate the pandemic. Though we are often heartened by human resilience in response to death and other hardships, for some, the burden of this pandemic will be too much. Among other mental health problems, we will likely see an increase in prolonged grief disorder. In this commentary, we review the new diagnosis of prolonged grief disorder and outline why we might anticipate increased rates of this condition on the heels of COVID-19, especially among older persons. We suggest ways we might mitigate this emerging problem.

negative: The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia PURPOSE: Severe ARDS is often associated with refractory hypoxemia, and early identification and treatment of hypoxemia is mandatory. For the management of severe ARDS ventilator settings, positioning therapy, infection control, and supportive measures are essential to improve survival. METHODS AND RESULTS: A precise definition of life-threating hypoxemia is not identified. Typical clinical determinations are: arterial partial pressure of oxygen < 60 mmHg and/or arterial oxygenation < 88 % and/or the ratio of PaO(2)/FIO(2) < 100. For mechanical ventilation specific settings are recommended: limitation of tidal volume (6 ml/kg predicted body weight), adequate high PEEP (>12 cmH(2)O), a recruitment manoeuvre in special situations, and a ‘balanced’ respiratory rate (20-30/min). Individual bedside methods to guide PEEP/recruitment (e.g., transpulmonary pressure) are not (yet) available. Prone positioning [early (≤ 48 hrs after onset of severe ARDS) and prolonged (repetition of 16-hr-sessions)] improves survival. An advanced infection management/control includes early diagnosis of bacterial, atypical, viral and fungal specimen (blood culture, bronchoalveolar lavage), and of infection sources by CT scan, followed by administration of broad-spectrum anti-infectives. Neuromuscular blockage (Cisatracurium ≤ 48 hrs after onset of ARDS), as well as an adequate sedation strategy (score guided) is an important supportive therapy. A negative fluid balance is associated with improved lung function and the use of hemofiltration might be indicated for specific indications. CONCLUSIONS: A specific standard of care is required for the management of severe ARDS with refractory hypoxemia.

negative: SARS-CoV-2 Isolation and Propagation from Turkish COVID-19 patients The novel coronavirus pneumonia, which was named later as Coronavirus Disease 2019 (COVID-19), is caused by the Severe Acute Respiratory Syndrome Coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. Today, over ninety thousand cases in Turkey, and two million cases around the world have been declared. Due to the urgent need for vaccine and anti-viral drug, isolation of the virus is crucial. Here, we report one of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology, and cell culture tropism of the virus that will be available to the research communities. Article Summary Scientists have isolated virus from Turkish COVID-19 patients. The isolation, propagation, and plaque and immune response assays of the virus described here will serve in following drug discovery and vaccine testing.

negative: Letter to the editor: Plenty of coronaviruses but no SARS-CoV-2

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: The Covid-Shock Doctrine: Under the Tutorship of CoV-2, the Voice(s) From Poland These are two autoethnographic voices. We speak in a strange time: democracy dies, social justice dies. A lot of people have died of the virus, many die of fear. We write to protest against new neoliberal and neoconservative “shock doctrine.” We write together to protest against destructive self-absorption, isolation, and fear. It is protest-text. But we are not sure what we can do now.

negative: Underreporting of death by COVID-19 in Brazil's second most populous state The COVID-19 pandemic brings to light the reality of the Brazilian health system. The underreporting of COVID-19 deaths in the state of Minas Gerais (MG), where is concentrated the second largest population of the country, reveals government unpreparedness, as there is a low capacity of testing in the population, which prevents the real understanding of the general panorama of Sars-Cov-2 dissemination. The goals of this research are to analyze the causes of deaths in the different Brazilian government databases (ARPEN and SINAN) and to assess whether there are sub-records shown by the unexpected increase in the frequency of deaths from causes clinically similar to COVID-19. A descriptive and quantitative analysis of the number of COVID-19 deaths and similar causes was made in different databases. Ours results demonstrate that the different official sources had a discrepancy of 209.23% between these data referring to the same period. There was also a 648.61% increase in SARS deaths in 2020, when compared to the average of previous years. Finally, it was shown that there was an increase in the rate of pneumonia and respiratory insufficiency (RI) by 5.36% and 5.72%, respectively. In conclusion, there is an underreporting of COVID-19 deaths in MG due to the unexplained excess of SARS deaths, Respiratory insufficiency and pneumonia compared to previous years.

negative: Expected impact of COVID-19 outbreak in a major metropolitan area in Brazil In January 2020 China reported to the World Health Organization an outbreak of pneumonia of undetermined origin in the city of Wuhan, Hubei. In January 30, 2020, the World Health Organization declared the outbreak of COVID-19 as a Public Health Emergency of International Interest (PHEI). Objectives: The aim of this study is to assess the impact of a COVID-19 epidemic in the metropolitan region of Sao Paulo, Brazil. Methods: We used a generalized SEIR (Susceptibles, Exposed, Infectious, Recovered) model, with additional Hospitalized variables (SEIHR model) and age-stratified structure to analyze the expected time evolution during the onset of the epidemic in the metropolitan area of Sao Paulo. The model allows to determine the evolution of the number of cases, the number of patients admitted to hospitals and deaths caused by COVID-19. In order to investigate the sensibility of our results with respect to parameter estimation errors we performed Monte Carlo analysis with 100 000 simulations by sampling parameter values from an uniform distribution in the confidence interval. Results: We estimate 1 368 (IQR: 880, 2 407) cases, 301 (22%) in older people (more than 60 years), 81 (50, 143) hospitalizations, and 14 (9, 26) deaths in the first 30 days, and 38 583 (IQR: 16 698, 113, 163) cases, 8 427 (21.8%) in older people (more than 60 years), 2181 (914, 6392) hospitalizations, and 397(166, 1205) deaths in the first 60 days. Limitations: We supposed a constant transmission probability Pc among different age-groups, and that every severe and critic case will be hospitalized, as well as that the detection capacity in all the primary healthcare services does not change during the outbreak. Conclusion: Supposing the reported parameters in the literature apply in the city of Sao Paulo, our study shows that it is expected that the impact of a COVID-19 outbreak will be important, requiring special planning from the authorities. This is the first study for a major metropolitan center in the south hemisphere, and we believe it can provide policymakers with a prognosis of the burden of the pandemic not only in Brazil, but also in other tropical zones, allowing to estimate total cases, hospitalization, and deaths, in support to the management of the public health emergence caused by COVID-19.

negative: Viable circulating endothelial cells and their progenitors are increased in Covid-19 patients During the course of Covid-19, the disease caused by the new Coronavirus SARS-CoV-2, thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. Circulating endothelial cells (CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious and cancer diseases. Using a validated flow cytometry procedure, we found that viable CEPs/mL were significantly increased in Covid-19 patients compared to healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CECs, in Covid-19 patients their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CEC ratio was significantly different. Both mild and severe Covid-19 patients had significantly more viable CECs compared to healthy controls. Patients who recovered had significantly less CECs/mL when compared to controls as well as to mild and severe Covid-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs/mL in severe Covid-19 patients. These findings suggest that CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in Covid-19 patients.

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: Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan, China in December 2019 and has put the world on alert. To safeguard Chinese citizens and to strengthen global health security, China has made great efforts to control the epidemic. Many in the global community have joined China to limit the epidemic. However, discrimination and prejudice driven by fear or misinformation have been flowing globally, superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts. We analyze this phenomenon and its underlying causes and suggest practical solutions.

negative: Coronavirus disease 2019: reassembly attack of coronavirus. There have been three major global outbreaks of acute respiratory disease caused by coronavirus in the last two decades. The ongoing Coronavirus Disease 2019 (COVID-19) first emerged in Wuhan, China, is the most dangerous, which spread to 163 countries and 6 continents and caused a major public health emergency worldwide. The outbreak is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) originated from bats, which spreads rapidly from human to human. As of 17 March 2020, there have been 179,112 confirmed cases and 7426 deaths worldwide, with a mortality rate of 4.1%. There is currently no effective treatment or approved vaccine, so isolating the source of infection and blocking the routes of transmission is important. In this article, we summarized the worldwide epidemic trend of COVID-19 and discussed its epidemiological characteristics, prevention and control measures. We hope this article could provide experience and help for global epidemic prevention and control.

negative: Bereavement support on the frontline of COVID-19: Recommendations for hospital clinicians Abstract Deaths due to COVID-19 are associated with risk factors which can lead to prolonged grief disorder, post-traumatic stress and other poor bereavement outcomes among relatives, as well as moral injury and distress in frontline staff. Here we review relevant research evidence, and provide evidence-based recommendations and resources for hospital clinicians to mitigate poor bereavement outcomes and support staff. For relatives, bereavement risk factors include dying in an intensive care unit, severe breathlessness, patient isolation or restricted access, significant patient and family emotional distress, and disruption to relatives’ social support networks. Recommendations include advance care planning; proactive, sensitive and regular communication with family members alongside accurate information provision; enabling family members to say goodbye in person where possible; supporting virtual communication; providing excellent symptom management and emotional and spiritual support; and providing and/or sign-posting to bereavement services. To mitigate effects of this emotionally challenging work on staff, we recommend an organisational and systemic approach which includes access to informal and professional support.

negative: Data-Driven Study of the COVID-19 Pandemic via Age-Structured Modelling and Prediction of the Health System Failure in Brazil amid Diverse Intervention Strategies In this work we propose a data-driven age-structured census-based SIRD-like epidemiological model capable of forecasting the spread of COVID-19 in Brazil. We model the current scenario of closed schools and universities, social distancing of individuals above sixty years old and voluntary home quarantine to show that it led to a considerable reduction in the number of infections as compared with a scenario without any control measures. Notwithstanding, our model predicts that the current measures are not enough to avoid overloading the health system, since the demand for intensive care units will soon surpass the number available. We also show that an urgent intense quarantine might be the only solution to avoid this scenario and, consequently, minimize the number of severe cases and deaths. On the other hand, we demonstrate that the early relaxation of the undergoing isolation measures would lead to an increase of millions of infections in a short period of time and the consecutive collapse of the health system.

negative: Potential neurological impact of coronaviruses: implications for the novel SARS-CoV-2. Coronaviruses (CoV) are viruses widely known to cause severe respiratory distress due to the prominent clinical symptoms presented. These symptoms, which include fever and dry cough, are frequently found in individuals with CoV infection. Neurological manifestations of CoV have often been neglected; however, recent studies have reported neurological consequences of CoV infection. Here, we review these literatures and discuss the neurologic impact of CoV while highlighting potential implications of the novel SARS-CoV-2 in the nervous system. We also discuss the possible routes by which these viruses invade the nervous system and the mechanism by which they may induce neurological damage.

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: Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020. An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.

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: COVID-19 is not just a flu. Learn from Italy and act now

negative: Die Auswirkungen der SARS-CoV-2-Pandemie auf die Sporttraumatologie

negative: Sports-Related Injuries and Deaths Physical activity in children and adolescents should be strongly encouraged. While there is a very low risk of death associated with participation in athletics within this age group, the epidemic of childhood obesity and sedentary lifestyle must be combated to ensure the long-term health and quality of life of today’s youth. Sports-related deaths due to trauma are usually readily identified; others require careful examination, adjunctive testing, and/or the expertise of consultants. A thorough investigation of circumstances surrounding the death, review of the medical records, and autopsy is mandated in these cases.

negative: Comprehensive Investigation and Isolation have Effectively Suppressed the Spread of COVID-19 The outbreak of COVID-19 since Dec. 2019 has caused severe life and economic damage worldwide, many countries are trapped by medical resource constraints or absence of targeted therapeutics, and therefore the implement of systemic policies to block this pandemic should be prioritized. Based on the transmission mechanisms and physicochemical properties of betacoronaviruses, we construct a fine-grained transmission dynamics model (ICRD) to forecast the crucial information of public concern, therein using dynamical coefficients to quantify the impact of the implement time and intensity of containment policies on the spread of epidemic. We find that the comprehensive investigation policy for susceptible population and the quarantine for suspected cases eminently contribute to reduce casualties during the phase of the dramatic increase of diagnosed cases. Statistic evidences strongly suggest that society should take such forceful public health interventions to cut the infection channels in the initial stage until the pandemic is interrupted.

negative: How will country-based mitigation measures influence the course of the COVID-19 epidemic?

negative: SARS, emerging infections, and bioterrorism preparedness

negative: Links between air pollution and COVID-19 in England In December 2019 a novel disease [coronavirus disease 19 (COVID-19) emerged in the Wuhan province of the People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) thought to have jumped species, from another mammal to humans. A pandemic caused by this virus is running rampant throughout the world. Thousands of cases of COVID-19 are reported in England and over 10,000 patients have died. Whilst there has been progress in managing this disease, it is not clear which factors, besides age, affect the severity and mortality of COVID-19. A recent analysis of COVID-19 in Italy identified links between air pollution and death rates. Here, we explored the correlation between three major air pollutants linked to fossil fuels and SARS-CoV-2 lethality in England. We compare up-to-date, real-time SARS-CoV-2 cases and death measurements from public databases to air pollution data monitored across over 120 sites in different regions. We found that the levels of some markers of poor air quality, nitrogen oxides and ozone, are associated with COVID-19 lethality in different English regions. We conclude that the levels of some air pollutants are linked to COVID-19 cases and morbidity. We suggest that our study provides a useful framework to guide health policy in countries affected by this pandemic.

negative: Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences

negative: Regulation and Trust: 3-Month Follow-up Study on COVID-19 Mortality in 25 European Countries BACKGROUND: The outbreak of the coronavirus disease (COVID-19) has dramatically changed societies in 2020. Since the end of February, Europe has been hit particularly hard by COVID-19, but there are major country differences in both the spread of the virus and measures taken to stop the virus. Social psychological factors such as institutional trust could be important in understanding the development of the epidemic. OBJECTIVE: The aim of this study was to examine country variations of COVID-19 mortality in Europe by analyzing social risk factors explaining the spread of the disease, restrictions and control measures, and institutional trust. METHODS: The present study was based on a background analysis of European Social Survey data on 25 European countries (N=47,802). Multilevel mixed effects linear regression models focused on 84 days of the COVID-19 epidemic (January 22 to April 14, 2020) and modelled the daily COVID-19 mortality. Analysis focused on the impact of social relations, restrictions, and institutional trust within each country. RESULTS: The spread of the COVID-19 epidemic has been fast everywhere, but the findings revealed significant differences between countries in COVID-19 mortality. Perceived sociability predicted higher COVID-19 mortality. Major differences between the 25 countries were found in reaction times to the crisis. Late reaction to the crisis predicted later mortality figures. Institutional trust was associated with lower COVID-19 mortality. CONCLUSIONS: The analyses demonstrated the importance of societal and social psychological factors in the spread of the COVID-19 epidemic. By considering multiple perspectives, this study showed that country differences in Europe are major, and this will have an impact on how countries will cope with the ongoing crisis in the following months. The results indicated the importance of timely restrictions and cooperation with people.

negative: The Courage to Change the Rules: A Proposal for an Essential Health R&D Treaty The medical needs of many of the world's population go unmet. A new treaty on essential health R&D could provide a binding framework to redirect today's scientific expertise to priority needs

negative: COVID-19 in Colombia endpoints. Are we different, like Europe? Abstract The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1), the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy.

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: Population-Level Mortality Rates from Novel Coronavirus (COVID-19) in South Korea Background: South Korea was among the first countries to report a case of the novel coronavirus (COVID-19) outside of China. As of 22 March, 2020, South Korea reported 8897 confirmed cases of and 104 deaths from COVID-19. Methods: We collected the number of laboratory-confirmed cases and deaths in South Korea from the World Health Organization (as of 21 March, 2020) and case distribution and fatality rates by age from the Korean Center for Disease Control and Prevention (as of 22 March, 2020). We estimated population-level mortality rates by fitting a negative binomial regression model with the number of deaths as the outcome and population by age as an offset. We then calculated the age-standardized death rate (ASDR) based on the current COVID-19 figures and for alternative scenarios of increased prevalence. Findings: The COVID-19 population-level mortality rate (per 100,000 person-years) increased with age: from 0.1 deaths among 30-39 year olds to 9.5 deaths among ≥80 year olds. The ASDR (per 100,000 person-years) was 0.8 deaths. The ASDR would increase to 52.0 deaths at a 1% prevalence (becoming the third leading cause of death) and 155.9 deaths at 3% prevalence (becoming the leading cause of death). Interpretation: Currently, the population-level mortality burden of COVID-19 in South Korea, as measured by the ASDR, was relatively low compared to other causes of death partly due to the low prevalence of COVID-19. If the prevalence increases from another outbreak, the mortality burden could increase substantially and surpass other leading causes.

negative: Flu or a Bug? Of late, apart from the four calendar seasons, there is yet another season referred to as the “flu season.” During this time of the year, we routinely hear the phrase “the flu is going around.” I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word “bug” is used so callously by adults that it has been registered wrongly in the minds of the little ones.

negative: Tackling the Global Challenge: Humanitarian Catastrophes “Humanitarian catastrophes,” conflicts and calamities generating both widespread human suffering and destructive events, require a wide range of emergency resources. This paper answers a number of questions that humanitarian catastrophes generate: Why and how do the most-developed countries—those with the resources, capabilities, and willingness to help—intervene in specific types of disasters? What ethical and legal guidelines shape our interventions? How well do we achieve our goals? It then suggests a number of changes to improve humanitarian responses, including better NGO-government cooperation, increased research on the best disaster response methods, clarification of the criteria and roles for humanitarian (military) interventions, and development of post-2015 Millennium Development Goals with more accurate progress measures.

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: Rapid estimation of excess mortality in times of COVID-19 in Portugal - Beyond reported deaths Background: One month after the first COVID-19 infection was recorded, Portugal counted 18 051 cases and 599 deaths from COVID-19. To understand the overall impact on mortality of the pandemic of COVID-19, we estimated the excess mortality registered in Portugal during the first month of the epidemic, from March 16 until April 14 using two different methods. Methods: We compared the observed and expected daily deaths (historical average number from daily death registrations in the past 10 years) and used 2 standard deviations confidence limit for all-cause mortality by age and specific mortality cause, considering the last 6 years. An adapted ARIMA model was also tested to validate the estimated number of all-cause deaths during the study period. Results: Between March 16 and April 14, there was an excess of 1,255 all-cause deaths, 14% more than expected. The number of daily deaths often surpassed the 2 standard deviations confidence limit. The excess mortality occurred mostly in people aged 75+. Forty-nine percent (49%) of the estimated excess deaths were registered as due to COVID-19, The other 51% registered as other natural causes. Conclusion: Even though Portugal took early containment measures against COVID-19, and the population complied massively with those measures, there was significant excess mortality during the first month of the pandemic, mostly among people aged 75+. Only half of the excess mortality was registered as directly due do COVID-19.

negative: COVID-19 outbreak: less stethoscope, more ultrasound

negative: News from the front: Excess mortality and life expectancy in two major epicentres of the COVID-19 pandemic in Italy Existing studies commonly rely on national official reports to estimate the impact of COVID-19 on population health and human life. However, relying on national reports is problematic because classification and estimation of COVID-19 mortality are not consistent across countries. Likewise, delay coronavirus test results and shortage of testing kits can result in undercounting of coronavirus deaths. To overcome these problems, this study exploits all cause daily death registrations data provide by the Italian Statistical Office (ISTAT) from 1st January to 4th April 2020. This allows us to: 1) calculate excess mortality in 2020 compared to the years 2015 to 2019; and 2) estimate life expectancy on a seasonal and annual basis. We focus our analysis on Bergamo and Brescia, the two hardest hit provinces in Lombardy, northern Italy. Given the clustering nature of the epidemic, focusing on the areas with high concentration of severe illness and deaths allows us to capture the true impact of COVID-19 on mortality and life expectancy, which are likely to be underestimated in the national level data. We find that on the period 1 Jan to 4 April 2020, seasonal life expectancy in Bergamo reduced by around 8.1 and 6.5 years compared to 2019 for men and women respectively (4.5 and 3.4 years in Brescia). The drop in period life expectancy for 2020 may total up to 3 years in the case of men and 2 years in the case of women. Such a sharp decrease in life expectancy has not been experienced in modern history since the Second World War. This study shows that, in the absence of public health interventions to reduce the spread of the virus, COVID-19 has set life expectancy in Bergamo and Brescia back to the Italian life expectancy of 15 years ago.

negative: Rapid community-driven development of a SARS-CoV-2 tissue simulator The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors like diabetes. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interactions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving rapid refinements with a two-to-four week release cycle. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health.

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 PaO(2)/FiO(2) (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 PaO(2)/FiO(2) 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: 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: Midwives in a pandemic: A call for solidarity and compassion

negative: [Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future]. The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.

negative: Transportation: Travel by Air, Car, and Train This chapter deals with issues of transportation and how they interact with the world of tourism security. The chapter examines such issues as air transportation security and safety, issues of fire at airport terminals, and issues of health and international travel, both from the perspective of the traveler and from the perspective of the host community. The chapter also examines some of the issues dealing with both train travel and motor coach travel and develops a template for how tourism security professionals need to deal with these issues.

negative: Bacterial Infections and the Respiratory Microbiome Cystic fibrosis (CF) is a genetic, multisystem disease due to defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an anion channel responsible for chloride and bicarbonate trafficking. Although this channel is expressed in many tissues, its impaired function in airway epithelial cells leads to hyperviscous mucous secretions impeding effective mucociliary clearance. Impaired clearance of inhaled microorganisms results in the establishment of chronic infection, triggering an overexaggerated inflammatory response. The resulting release of inflammatory cytokines and enzymes causes pulmonary damage in the form of bronchiectasis, further impairing mucociliary action, forming a vicious cycle. Subsequent respiratory failure remains the leading cause of death in individuals with CF.

negative: Forecasting the dynamics of COVID-19 Pandemic in Top 15 countries in April 2020: ARIMA Model with Machine Learning Approach We here predicted some trajectories of COVID-19 in the coming days (until April 30, 2020) using the most advanced Auto-Regressive Integrated Moving Average Model (ARIMA). Our analysis predicted very frightening outcomes, which defines to worsen the conditions in Iran, entire Europe, especially Italy, Spain, and France. While South Korea, after the initial blast, has come to stability, the same goes for the COVID-19 origin country China with more positive recovery cases and confirm to remain stable. The United States of America (USA) will come as a surprise and going to become the epicenter for new cases during the mid-April 2020. Based on our predictions, public health officials should tailor aggressive interventions to grasp the power exponential growth, and rapid infection control measures at hospital levels are urgently needed to curtail the COVID-19 pandemic.

negative: Why We (Probably) Must Deliberately Infect In the grip of a pandemic of proportions that have not been seen for generations, some have proposed conducting “human challenge” vaccine trials in which healthy volunteers are deliberately infected with the SARS-CoV-2 virus that causes COVID-19. Such trials might substantially speed up the search for a safe and effective vaccine and save many thousands of lives. I argue that such trials are not only permissible, but given reasonable assumptions, they are morally required, subject to some important caveats.

negative: Open Data Resources for Fighting COVID-19 We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.

negative: The first case of COVID-19 treated with the complement C3 inhibitor AMY-101 Abstract Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a “cytokine storm” involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.

negative: [Management and clinical thinking of Coronavirus Disease 2019] In December 2019, the 2019 novel coronavirus pneumonia (NCP, officially named Coronavirus Disease 2019(COVID-19) by the World Health Organization) broke out in Wuhan, Hubei, and it quickly spread to the whole country and abroad. The situation was at stake. The sudden and serious COVID-19 epidemic has brought us a lot of urgent problems. How to effectively control the spread of COVID-19? When does the population infection rate rise to its peak? What will eventually be the number of infected patients? How to make early diagnosis? What effective antiviral drugs are available? How to effectively treat with existing drugs? Can it successfully improve the survival rate of critically patients? In response to the above questions, we put forward corresponding suggestions and reflections from the perspective of the infectious clinician.

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: Estimating the early death toll of COVID-19 in the United States BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5–3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.

negative: COVID-19 and potential global mortality - Revisited

negative: Analysis and forecast of COVID-19 spreading in China, Italy and France Abstract In this note we analyze the temporal dynamics of the coronavirus disease 2019 outbreak in China, Italy and France in the time window 22 / 01 − 15 / 03 / 2020 . A first analysis of simple day-lag maps points to some universality in the epidemic spreading, suggesting that simple mean-field models can be meaningfully used to gather a quantitative picture of the epidemic spreading, and notably the height and time of the peak of confirmed infected individuals. The analysis of the same data within a simple susceptible-infected-recovered-deaths model indicates that the kinetic parameter that describes the rate of recovery seems to be the same, irrespective of the country, while the infection and death rates appear to be more variable. The model places the peak in Italy around March 21st 2020, with a peak number of infected individuals of about 26000 (not including recovered and dead) and a number of deaths at the end of the epidemics of about 18,000. Since the confirmed cases are believed to be between 10 and 20% of the real number of individuals who eventually get infected, the apparent mortality rate of COVID-19 falls between 4% and 8% in Italy, while it appears substantially lower, between 1% and 3% in China. Based on our calculations, we estimate that 2500 ventilation units should represent a fair figure for the peak requirement to be considered by health authorities in Italy for their strategic planning. Finally, a simulation of the effects of drastic containment measures on the outbreak in Italy indicates that a reduction of the infection rate indeed causes a quench of the epidemic peak. However, it is also seen that the infection rate needs to be cut down drastically and quickly to observe an appreciable decrease of the epidemic peak and mortality rate. This appears only possible through a concerted and disciplined, albeit painful, effort of the population as a whole.

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: The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern However, no specific antiviral treatments or vaccines are available yet This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2 An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020) The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China1 A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China2 COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3 0 days (range, 0 to 24 0), and the time from symptom onset to developing pneumonia is 4 0 days (range, 2 0 to 7 0)3 Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role3 Fever, dry cough, and fatigue are common symptoms at onset of COVID-194 Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans4,5 No specific antiviral treatments or vaccines are available because it is a new emerging viral disease Development of SARS-CoV-2-based vaccines is urgently required The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines6 The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no MN908947 3)7 Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and β-propiolactone8 The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus9 Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table 1) Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered

negative: Coronary plague instability in severe acute respiratory syndrome Abstract In his second week of severe acute respiratory syndrome (SARS) illness, a patient developed an unusually complicated course of acute coronary syndrome. One day after initial stabilization of a non-ST-elevated anterior myocardial infarction (MI), he sustained an ST-elevated anterior MI. Eight hours after emergency coronary intervention to the culprit lesion, he developed another ST-elevated MI in the inferior territory. Acute inflammation and cytokine storm in the immunopathological phase of SARS may play a role in coronary plague instability. Physicians should be alert to this potentially fatal complication and adopt appropriate vigilant and aggressive management strategies.

negative: Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms [Image: see text] The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

negative: Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size Abstract Objectives: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). Design and methods: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. Results: Patients with AMI showed significantly higher serum IP-10 levels (137.5±79.8 pg/mL) than control subjects (91.2±40.1 pg/mL) and patients with AP (93.3±41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. Conclusions: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.

negative: Risk for Transportation of 2019 Novel Coronavirus (COVID-19) from Wuhan to Cities in China On January 23, 2020, China quarantined Wuhan to contain an emerging coronavirus (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 cities in China before the quarantine. The expected risk is >50% in 130 (95% CI 89–190) cities and >99% in the 4 largest metropolitan areas of China.

negative: COVID-19 randomised trial protocols: rapid publication without barriers

negative: Causes and characteristics of death in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: a retrospective cohort study BACKGROUND: Acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are associated with high in-hospital mortality. However, in cohorts of ARDS patients from the 1990s, patients more commonly died from sepsis or multi-organ failure rather than refractory hypoxemia. Given increased attention to lung-protective ventilation and sepsis treatment in the past 25 years, we hypothesized that causes of death may be different among contemporary cohorts. These differences may provide clinicians with insight into targets for future therapeutic interventions. METHODS: We identified adult patients hospitalized at a single tertiary care center (2016–2017) with AHRF, defined as PaO(2)/FiO(2) ≤ 300 while receiving invasive mechanical ventilation for > 12 h, who died during hospitalization. ARDS was adjudicated by multiple physicians using the Berlin definition. Separate abstractors blinded to ARDS status collected data on organ dysfunction and withdrawal of life support using a standardized tool. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: We identified 385 decedents with AHRF, of whom 127 (33%) had ARDS. The most common primary causes of death were sepsis (26%), pulmonary dysfunction (22%), and neurologic dysfunction (19%). Multi-organ failure was present in 70% at time of death, most commonly due to sepsis (50% of all patients), and 70% were on significant respiratory support at the time of death. Only 2% of patients had insupportable oxygenation or ventilation. Eighty-five percent died following withdrawal of life support. Patients with ARDS more often had pulmonary dysfunction as the primary cause of death (28% vs 19%; p = 0.04) and were also more likely to die while requiring significant respiratory support (82% vs 64%; p < 0.01). CONCLUSIONS: In this contemporary cohort of patients with AHRF, the most common primary causes of death were sepsis and pulmonary dysfunction, but few patients had insupportable oxygenation or ventilation. The vast majority of deaths occurred after withdrawal of life support. ARDS patients were more likely to have pulmonary dysfunction as the primary cause of death and die while requiring significant respiratory support compared to patients without ARDS.

negative: Characterization of the 3a Protein of SARS-associated Coronavirus in Infected Vero E6 Cells and SARS Patients Abstract Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.

negative: Public views of the uk media and government reaction to the 2009 swine flu pandemic BACKGROUND: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. METHODS: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. RESULTS: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. CONCLUSIONS: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.

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: Projektion der COVID-19-Epidemie in Deutschland The authors model the evolution of the number of confi rmed cases of COVID-19 in Germany. Their theoretical framework builds on a continuous time Markov chain with four physical states: healthy, sick, recovered or asymptomatic infected, and dead. Their quantitative solution matches the number of sick individuals based on the most recent fi gures with the share of sick individuals following from infection rates and sickness probabilities. They employ this framework to study the expected peak of the number of sick individuals in a scenario without public regulation of social contacts. They also study the impact of public regulations. For all scenarios, they report the expected end of the COVID-19 epidemic.

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: Prävention von Infektionskrankheiten in Industrieländern Prevention of infectious diseases is targeted at individuals, specific risk groups or communities. Vaccines are one of the most cost-effective medical interventions and protect the individual and the community against vaccine preventable diseases. Immunization programs aim to control, eliminate or eradicate infectious pathogens. In industrialized countries several vaccine preventable diseases are almost eliminated. Strict implementation of recommendations for influenza and pneumococcal immunization is crucial to reduce morbidity and mortality. Hence, uptake of recommended immunization among adults and elderly people is often low. Internal specialists are demanded to improve vaccine coverage in those age groups.

negative: Global epidemiology of coronavirus disease 2019 (COVID-19): disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.

negative: Transmission and epidemiological characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19): preliminary evidence obtained in comparison with 2003-SARS Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia (COVID-19) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19. Methods: The information of COVID-19 and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases were analyzed. The information of 853 confirmed COVID-19 patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 case data. Results: The growth rate of new cases and deaths of COVID-19 were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 cases aged 1 months to 94 years and the average age was (45.05 ± 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 patients is higher than that of secondary cases.

negative: Public perception and attitudes to disaster risks in a coastal metropolis of Saudi Arabia Abstract Disaster risk reduction is an increasingly important policy issue, especially in developing countries that suffer most of the global human and economic losses associated with disasters. Indeed, public awareness and attitudes can help in disaster risk reduction and management efforts toward reducing mortality and economic losses. In Saudi Arabia, many cities have been recently experiencing incidences of disasters, such as floods, disease epidemics, and sandstorms. However, studies on public perception of disaster risk in the country are few and nascent. Therefore, based on a questionnaire survey (n = 683), this paper explores public perception and attitudes to disaster risks in Dammam, a coastal metropolis in Saudi Arabia. The findings indicate that although almost two-thirds (64.7%) of the participants are aware of disasters, and 81% are concerned about disaster risks, less than half (47.3%) believe that their settlements could be at risk. While 37% opine that disasters are caused by both natural factors and human activities, about half (54%) indicate that they can personally contribute to reducing disaster risks. Chi-square analysis indicates a significant positive relationship between place of residence and perception of disaster risks (χ2 (6) = 56.18, p < 0.05), and between place of residence and concern about disaster risks (χ2 (12) = 68.47, p < 0.05). The paper recommends raising public awareness and encouraging positive behaviors in reducing disaster risks in the study area and similar environments.

negative: Impacto de la pandemia COVID-19 en el servicio de urología de un centro de referencia en la Comunidad de Madrid Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has caused tens of thousands of deaths in Spain and has managed to breakdown the healthcare system hospitals in the Community of Madrid, largely due to its tendency to cause severe pneumonia, requiring ventilatory support. This fact has caused our center to collapse, with 130% of its beds occupied by COVID-19 patients, thus causing the absolute cessation of activity of the urology service, the practical disappearance of resident training programs, and the incorporation of a good part of the urology staff into the group of medical personnel attending these patients. In order to recover from this extraordinary level of suspended activity, we will be obliged to prioritize pathologies based on purely clinical criteria, for which tables including the relevance of each pathology within each area of urology are being proposed. Technology tools such as online training courses or surgical simulators may be convenient for the necessary reestablishment of resident education.

negative: Estimation of the case fatality rate based on stratification for the COVID-19 outbreak This work is motivated by the recent worldwide pandemic of the novel coronavirus disease (COVID-19). When an epidemiological disease is prevalent, estimating the case fatality rate, the proportion of deaths out of the total cases, accurately and quickly is important as the case fatality rate is one of the crucial indicators of the risk of a disease. In this work, we propose an alternative estimator of the case fatality rate that provides more accurate estimate during an outbreak by reducing the downward bias (underestimation) of the naive CFR, the proportion of deaths out of confirmed cases at each time point, which is the most commonly used estimator due to the simplicity. The proposed estimator is designed to achieve the availability of real-time update by using the commonly reported quantities , the numbers of confirmed, cured, deceased cases, in the computation. To enhance the accuracy, the proposed estimator adapts a stratification, that allows the estimator to use information from heterogeneous strata separately. With the COVID-19 cases of China, South Korea and the United States, we numerically show the proposed stratification-based estimator plays a role of providing an early warning about the severity of a epidemiological disease that estimates the final case fatality rate accurately and shows faster convergence to the final case fatality rate.

negative: Health Psychology The chapter draws parallels and contrasts between the study of health in North American and other industrialized countries and health of people living in developing countries, which comprise 80% of the world’s population. Lessons are provided for three common health problems where psychologists play a major role within multidisciplinary teams. The lessons use published journal articles, web sites of international organizations, and the author’s personal experiences living and working in developing countries. One topic concerns the large number of women who unnecessarily die in childbirth and the non-medical reasons. The second is environmental health, which includes sources of clean water, waste disposal, and personal hygiene. Solving this problem requires behavior change. The third concerns child hunger and its disabling effects on cognitive development. The focus of this chapter is on examining the health problem within context and identifying solutions that work and do not work. Background is provided for the novice, so students learn the larger picture into which these issues fit, and how to apply the same analysis to other health problems.

negative: Estimating Preventable COVID19 Infections Related to Elective Outpatient Surgery in Washington State: A Quantitative Model Background: As the number of suspected and confirmed COVID19 cases in the US continues to rise, the US surgeon general, Centers for Disease Control and Prevention, and several specialty societies have issued recommendations to consider canceling elective surgeries. However, these recommendations have also faced controversy and opposition. Objective: The goal of this study is to provide a quantitative analysis and model for preventable COVID19 infections from elective outpatient or ambulatory surgery cases, which can also be adapted to analyze COVID19 transmission in other healthcare settings. Furthermore, given the controversy over the appropriate handling of elective surgical cases during this pandemic, we hope that our results may have a positive impact on health policy and public health. Methods: Using previously published information on elective ambulatory or outpatient surgical procedures and publicly available data on COVID19 infections in the US and on the Diamond Princess cruise ship, we calculated a transmission rate and generated a mathematical model to predict a lower bound for the number of healthcare-acquired COVID19 infections that could be prevented by canceling or postponing elective outpatient surgeries in Washington state. Results: Our model predicts that over the course of 30 days, at least 2445 preventable patient infections and at least 1557 preventable healthcare worker (HCW) infections would occur in WA state alone if elective outpatient procedures were to continue as usual. The majority of these infections are caused by transmission from HCW who became infected at work. Conclusion: Given the large numbers of COVID19 infections that could be prevented by canceling elective outpatient surgeries, our findings support the recommendations of the US Surgeon General, CDC, American College of Surgeons (ACS), American Society of Anesthesiologists (ASA), and Anesthesia Patient Safety Foundation (APSF) to consider rescheduling or postponing elective surgeries until the COVID19 pandemic is under better control in the US.

negative: Decontamination of Bacillus subtilis var. niger spores on selected surfaces by chlorine dioxide gas. OBJECTIVE Chlorine dioxide (CD) gas has been used as a fumigant in the disinfection of biosafety laboratories. In this study, some experiments were conducted to assess the inactivation of spores inoculated on six materials [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study were to determine the sporicidal efficacy of CD gas and the effect of prehumidification before decontamination on sporicidal efficacy. METHODS Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm×1.0 cm for PVC, GS, and CC) were contaminated with 10 μl of Bacillus subtilis var. niger (ATCC 9372) spore suspension in mixed organic burden and then dried in a biosafety cabinet for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction liquid for 1 h and then vortexing the liquid for 1 min. RESULTS The log reductions in spore numbers on inoculated test materials exposed to CD gas [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64. Statistically significant differences were found in decontamination efficacies on test material coupons of SS, PS, PU, and CC between with and without a 1-h prehumidification treatment. With the extraction method, there were no statistically significant differences in the recovery ratios between the porous and non-porous materials. CONCLUSIONS The results reported from this study could provide information for developing decontamination technology based on CD gas for targeting surface microbial contamination.

negative: Jetzt kommt es auf uns Hausärzte an!: Coronavirus in Deutschland Ausgangssperren, steigende Infektionszahlen, Angst in der Bevölkerung — die Coronavirus-Pandemie hält das ganze Land in Atem. Hausärzte müssen in dieser Situation das hohe Vertrauen nutzen, das sie genießen: Durch klar strukturierte, qualitativ hochwertige Versorgung, aber auch durch die Verbreitung von Ruhe und Zuversicht.

negative: The Potential Impact of Interruptions to HIV Services: A Modelling Case Study for South Africa The numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.

negative: Possible Association of Thymus Dysfunction with Fading Syndromes in Puppies and Kittens This article focuses on the role of the thymus gland in maintaining the health of young animals and on how thymus dysfunction may contribute to some cases of wasting and death. Current knowledge about thymus hormones is reviewed briefly, and one form of a wasting syndrome in pups that is responsive to thymus hormone therapy is described.

negative: Estimating and forecasting COVID-19 attack rates and mortality {We describe a model for estimating past and current infections as well as future deaths due to the ongoing COVID-19 pandemic. The model does not use confirmed case numbers and is based instead on recorded numbers of deaths and on the age-specific population distribution. A regularized deconvolution technique is used to infer past infections from recorded deaths. Forecasting is based on a compartmental SIR-type model, combined with a probability distribution for the time from infection to death. The effect of non-pharmaceutical interventions (NPIs) is modelled empirically, based on recent trends in the death rate. The model can also be used to study counterfactual scenarios based on hypothetical NPI policies.

negative: What We Know So Far (As of March 26, 2020) About COVID-19 – An MRT Point of View

negative: A study of non-prescription usage of antibiotics in the upper respiratory tract infections in the urban population

negative: Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV CORONAVIRUSES, like many animal viruses, are characterized by a restricted host range and tissue tropism(1). Transmissible gastroenteritis virus (TGEV), a major pathogen causing a fatal diarrhoea in newborn pig, replicates selectively in the differentiated enterocytes covering the villi of the small intestine(2). To investigate the molecular determinants of the infection, we characterized the surface molecule used by the virus for binding and entry into host cells. Here we report that aminopeptidase N, an ectoenzyme abundantly expressed at the apical membrane of the enterocytes, serves as a receptor for TGEV. Monoclonal antibodies were selected for their ability to block infection by TGEV of porcine cell lines. They recognized a brush-border membrane protein of M(r), 150K, which was identified as aminopeptidase N by ammo-terminal sequencing. Two lines of evidence supported the view that the peptidase itself acts as a receptor. First, virions bound specifically to aminopep-tidase N that was purified to homogeneity. Second, recombinant expression of aminopeptidase N conferred infectivity by TGEV to an otherwise non-permissive cell line.

negative: Epidemic size of novel coronavirus-infected pneumonia in the Epicenter Wuhan: using data of five-countries' evacuation action Background: Since late December 2019, novel coronavirus-infected pneumonia (NCP) emerged in Wuhan, Hubei province, China. Meanwhile, NCP rapidly spread from China to other countries, and several countries' government rush to evacuate their citizens from Wuhan. We analyzed the infection rate of the evacuees and extrapolated the results in Wuhan's NCP incidence estimation. Methods: We collected the total number and confirmed cases of 2019-nCov infection in the evacuation of Korea, Japan, Germany, Singapore, and France and estimated the infection rate of the 2019 novel coronavirus (2019-nCov) among people who were evacuated from Wuhan with a meta-analysis. NCP incidence of Wuhan was indirectly estimated based on data of evacuation. Results: From Jan 29 to Feb 2, 2020, 1916 people have been evacuated from Wuhan, among them 17 have been confirmed 2019-nCov infected. The infection rate is estimated to be 1.1% (95% CI 0.4%-3.1%) using one group meta-analysis method with random effect model. We then estimated that almost 110,000 (95% CI: 40,000-310,000) people were infected with 2019-nCov in Wuhan around Feb 2, 2020, assuming the infection risk of evacuees is close to Chinese citizens in Wuhan. Conclusions: At the beginning of the outbreak, incidence of NCP may be vastly underestimated. Our result emphasizes that 2019-nCov has proposed a huge public health threats in Wuhan. We need to respond more rapidly, take large-scale public health interventions and draconian measures to limiting population mobility and control the epidemic.

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: Replicative homeostasis II: Influence of polymerase fidelity on RNA virus quasispecies biology: Implications for immune recognition, viral autoimmunity and other "virus receptor" diseases Much of the worlds' population is in active or imminent danger from established infectious pathogens, while sporadic and pandemic infections by these and emerging agents threaten everyone. RNA polymerases (RNA(pol)) generate enormous genetic and consequent antigenic heterogeneity permitting both viruses and cellular pathogens to evade host defences. Thus, RNA(pol )causes more morbidity and premature mortality than any other molecule. The extraordinary genetic heterogeneity defining viral quasispecies results from RNA(pol )infidelity causing rapid cumulative genomic RNA mutation a process that, if uncontrolled, would cause catastrophic loss of sequence integrity and inexorable quasispecies extinction. Selective replication and replicative homeostasis, an epicyclical regulatory mechanism dynamically linking RNApol fidelity and processivity with quasispecies phenotypic diversity, modulating polymerase fidelity and, hence, controlling quasispecies behaviour, prevents this happening and also mediates immune escape. Perhaps more importantly, ineluctable generation of broad phenotypic diversity after viral RNA is translated to protein quasispecies suggests a mechanism of disease that specifically targets, and functionally disrupts, the host cell surface molecules – including hormone, lipid, cell signalling or neurotransmitter receptors – that viruses co-opt for cell entry. This mechanism – "Viral Receptor Disease (VRD)" – may explain so-called "viral autoimmunity", some classical autoimmune disorders and other diseases, including type II diabetes mellitus, and some forms of obesity. Viral receptor disease is a unifying hypothesis that may also explain some diseases with well-established, but multi-factorial and apparently unrelated aetiologies – like coronary artery and other vascular diseases – in addition to diseases like schizophrenia that are poorly understood and lack plausible, coherent, pathogenic explanations.

negative: Changing patterns of mortality during the COVID-19 pandemic: population-based modelling to understand palliative care implications Background COVID-19 has directly and indirectly caused high mortality worldwide. Aim To explore patterns of mortality during the COVID-19 pandemic and implications for palliative care provision, planning, and research. Design Descriptive analysis and population-based modelling of routine data. Participants and setting All deaths registered in England and Wales between 7th March and 15th May 2020. We described the following mortality categories by age, gender and place of death: 1) baseline deaths (deaths that would typically occur in a given period) 2) COVID-19 deaths 3) additional deaths not directly attributed to COVID-19. We estimated the proportion of COVID-19 deaths among people who would be in their last year of life in the absence of the pandemic, using simple modelling with explicit assumptions. Results During the first 10 weeks of the pandemic there were 101,615 baseline deaths, 41,105 COVID-19 deaths and 14,520 additional deaths. Deaths in care homes increased by 220% compared to home and hospital deaths which increased by 77% and 90%. Hospice deaths fell by 20%. Additional deaths were among older people (86% aged [≥]75 years), and most occurred in care homes (56%) and at home (43%). We estimate that 44% (38% to 50%) of COVID-19 deaths occurred among people who would have been in their last year of life in the absence of the pandemic. Conclusions Healthcare systems must ensure availability of palliative care to support people with severe COVID-19 in community and hospital settings. Integrated models of palliative care in care homes are urgently needed.

negative: Coronavirus disease 2019: The harms of exaggerated information and non‐evidence‐based measures The evolving coronavirus disease 2019 (COVID-19) epidemic1 is certainly cause for concern. Proper communication and optimal decision-making is an ongoing challenge, as data evolve. The challenge is compounded, however, by exaggerated information. This can lead to inappropriate actions. It is important to differentiate promptly the true epidemic from an epidemic of false claims and potentially harmful actions.

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: Impact of international travel dynamics on domestic spread of 2019-nCoV in India: origin-based risk assessment in importation of infected travelers The recent pandemic caused by the 2019 outbreak of novel coronavirus (2019-nCoV or COVID-19) has affected more than 3.0 million people resulting ~ 212,000 deaths across 215 countries/territories as on 28th April 2020. The importation of the cases owing to enormous international travels from the affected countries is the foremost reason for local cycle of transmission. For a country like India, the second most populous country in the world with ~ 1.35 billion population, the management and control of 2019-nCoV domestic spread heavily relied on effective screening and strict quarantine of passengers arriving at various international airports in India from affected countries. Here, by extracting the data from FLIRT, an online airline database for more than 800 airlines, and scanning more than 180,000 flights and 39.9 million corresponding passenger seats during 4th – 25th March, we show that India experienced the highest risk index of importing the passengers from middle eastern airports. Contrary to perception, travelers from China imposed lowest risk of importing the infected cases in India. This is clearly evident form the fact that while the number of infected cases were on the peak in China India was one of the least affected countries. The number of cases in India started exhibiting a sharp increase in the infected cases only after the European countries and USA recorded large number of infected cases. We further argue that while the number of cases in middle eastern countries may still be very low, the airports in middle eastern countries, particularly Dubai, being one of the largest transit hubs for international passengers, including arriving in India, might have posed a higher risk of getting infected with 2019-nCoV. We suggest that any future travel related disease infection screening at the airports should critically assess the passengers from major transit hubs in addition to affected country of origin.

negative: Saffold virus infection associated with human myocarditis Abstract Background Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been isolated from different anatomical compartments, including the myocardium, but, until now, it has not been possible to demonstrate the accompanying histopathological signs of inflammation. Objectives The aim of the study was to examine if saffold virus is capable of causing invasive infection in the human myocardium. Study design Using real-time PCR, we retrospectively examined formalin-fixed paraffin embedded cardiac tissue specimens from 150 deceased individuals diagnosed with myocarditis at autopsy. The results were compared with histological findings. Results and conclusions Saffold virus was detected in the myocardium, lung tissue and blood of one child and was accompanied by histopathological inflammation in the heart and lungs, which was supportive of a viral infection. These findings suggest that cardioviruses may be associated with myocarditis in humans.

negative: Coupling between death spikes and birth troughs. Part 1: Evidence Abstract In the wake of the influenza pandemic of 1889–1890 Jacques Bertillon, a pioneer of medical statistics, noticed that after the massive death spike there was a dip in birth numbers around 9 months later which was significantly larger than that which could be explained by the population change as a result of excess deaths. In addition it can be noticed that this dip was followed by a birth rebound a few months later. However having made this observation, Bertillon did not explore it further. Since that time the phenomenon was not revisited in spite of the fact that in the meanwhile there have been several new cases of massive death spikes. The aim here is to analyze these new cases to get a better understanding of this death–birth coupling phenomenon. The largest death spikes occurred in the wake of more recent influenza pandemics in 1918 and 1920, others were triggered by the 1923 earthquakes in Tokyo and the Twin Tower attack on September 11, 2001. We shall see that the first of these events indeed produced an extra dip in births whereas the 9/11 event did not. This disparity highlights the pivotal role of collateral sufferers. In the last section it is shown how the present coupling leads to predictions; it can explain in a unified way effects which so far have been studied separately, as for instance the impact on birth rates of heat waves. Thus, it appears that behind the apparent randomness of birth rate fluctuations there are in fact hidden explanatory factors.

negative: Non-COVID-19 Deaths After Social Distancing in Norway Lay persons and policy makers have speculated on how the imposition of social distancing to reduce SARS CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has affected non-COVID-19 (coronavirus disease of 2019) deaths. No rigorous estimation of the effect appears in the scholarly literature. We use time-series methods to compare non-COVID-19 deaths observed in Norway before and during the epidemic to those expected from non-COVID-19 deaths in Sweden as well as from the history of Norwegian mortality trends. We find that in the first 8 weeks after the divergence between Swedish and Norwegian policies (the only period for which dependable data can be had) approximately 650 fewer Norwegians died than expected.

negative: Features, Evaluation and Treatment Coronavirus (COVID-19) According to the World Health Organization (WHO), viral diseases continue to emerge and represent a serious issue to public health In the last twenty years, several viral epidemics such as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003, and H1N1 influenza in 2009, have been recorded Most recently, the Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 In a timeline that reaches the present day, an epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China's Hubei province, was first reported to the WHO Country Office in China, on December 31, 2019 Published literature can trace the beginning of symptomatic individuals back to the beginning of December 2019 As they were unable to identify the causative agent, these first cases were classified as "pneumonia of unknown etiology " The Chinese Center for Disease Control and Prevention (CDC) and local CDCs organized an intensive outbreak investigation program The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19 On February 11, 2020, the WHO Director-General, Dr Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a "COVID-19," which is the acronym of "coronavirus disease 2019" In the past twenty years, two additional coronavirus epidemics have occurred SARS-CoV provoked a large-scale epidemic beginning in China and involving two dozen countries with approximately 8000 cases and 800 deaths, and the MERS-CoV that began in Saudi Arabia and has approximately 2,500 cases and 800 deaths and still causes as sporadic cases This new virus seems to be very contagious and has quickly spread globally In a meeting on January 30, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission An additional landmark occurred on February 26, 2020, as the first case of the disease, not imported from China, was recorded in the United States Initially, the new virus was called 2019-nCoV Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs) The CoVs have become the major pathogens of emerging respiratory disease outbreaks They are a large family of single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species For reasons yet to be explained, these viruses can cross species barriers and can cause, in humans, illness ranging from the common cold to more severe diseases such as MERS and SARS Interestingly, these latter viruses have probably originated from bats and then moving into other mammalian hosts — the Himalayan palm civet for SARS-CoV, and the dromedary camel for MERS-CoV — before jumping to humans The dynamics of SARS-Cov-2 are currently unknown, but there is speculation that it also has an animal origin The potential for these viruses to grow to become a pandemic worldwide seems to be a serious public health risk Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the "very high" level, on February 28, 2020 Probably, the effects of the epidemic caused by the new CoV has yet to emerge as the situation is quickly evolving World governments are at work to establish countermeasures to stem possible devastating effects Health organizations coordinate information flows and issues directives and guidelines to best mitigate the impact of the threat At the same time, scientists around the world work tirelessly, and information about the transmission mechanisms, the clinical spectrum of disease, new diagnostics, and prevention and therapeutic strategies are rapidly developing Many uncertainties remain with regard to both the virus-host interac ion and the evolution of the epidemic, with specific reference to the times when the epidemic will reach its peak At the moment, the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing transmission in the community is our best weapon Aggressive isolation measures in China have led to a progressive reduction of cases in the last few days In Italy, in geographic regions of the north of the peninsula, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system In the midst of the crisis, the authors have chosen to use the "Statpearls" platform because, within the PubMed scenario, it represents a unique tool that may allow them to make updates in real-time The aim, therefore, is to collect information and scientific evidence and to provide an overview of the topic that will be continuously updated

negative: A tribute to frontline corona warriors––Doctors who sacrificed their life while saving patients during the ongoing COVID-19 pandemic

negative: Avian preparedness: simulations of bird diseases and reverse scenarios of extinction in Hong Kong, Taiwan, and Singapore This article describes relations between humans, animals, artefacts, and pathogens in simulations of disasters, taking bird diseases in three Chinese sentinel posts as ethnographic cases. Drawing on distinctions between simulation, ritual, and play, it shows that the engagement of actors in the imaginary of simulations, which they describe as ‘realism’, reflectively reverses the oppositions between humans and nonhumans, active and passive, fiction and reality that shape ordinary life. Borrowing from the anthropology of hunting societies, it argues that simulations of bird diseases, considered as signs of future species extinction, rely on cynegetic techniques of power, in which humans and animals symmetrically shift perspectives, and not only on pastoralist techniques, in which humans are above the population they monitor and sometimes sacrifice.

negative: Excess mortality in England and Wales during the first wave of the COVID-19 pandemic Background Deaths during the COVID-19 pandemic result directly from infection and exacerbation of other diseases and indirectly from deferment of care for other conditions, and are socially and geographically patterned. We quantified excess mortality in regions of England and Wales during the pandemic, for all causes and for non-COVID-19 associated deaths. Methods Weekly mortality data for 1 Jan 2010 to 1 May 2020 for England and Wales were obtained from the Office of National Statistics. Mean-dispersion negative binomial regressions were used to model death counts based on pre-pandemic trends and exponentiated linear predictions were subtracted from: i) all-cause deaths; and ii) all-cause deaths minus COVID-19 related deaths for the pandemic period (07-13 March to 25 April to 8 May). Findings Between 7 March and 8 May 2020, there were 47,243 (95%CI: 46,671 to 47,815) excess deaths in England and Wales, of which 9,948 (95%CI: 9,376 to 10,520) were not associated with COVID-19. Overall excess mortality rates varied from 49 per 100,000 (95%CI: 49 to 50) in the South West to 102 per 100,000 (95%CI: 102 to 103) in London. Non-COVID-19 associated excess mortality rates ranged from -1 per 100,000 (95%CI: -1 to 0) in Wales (i.e. mortality rates were no higher than expected) to 26 per 100,000 (95%CI: 25 to 26) in the West Midlands. Interpretation The COVID-19 pandemic has had markedly different impacts on the regions of England and Wales, both for deaths directly attributable to COVID-19 infection and for deaths resulting from the national public health response.

negative: Access to Care for Dementia patients suffering from COVID-19

negative: The Tsinghua–Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China

negative: Literature-related discovery: Potential treatments and preventatives for SARS Abstract Literature-related discovery (LRD) is the linking of two or more previously disjoint concepts in order to produce novel, interesting, plausible, and intelligible connections (i.e., potential discovery). LRD has been used to identify potential treatments or preventative actions for challenging medical problems, among myriad other applications. Severe acute respiratory syndrome (SARS) was the first pandemic of the 21st century. SARS was eventually controlled through increased hygienic measures (e.g., face mask protection, frequent hand washing, living quarter disinfection), travel restrictions, and quarantine. According to recent reviews of SARS, none of the drugs that were used during the pandemic worked. For the present paper, SARS was selected as the first application of LRD to an infectious disease. The main goal of this research was to identify non-drug non-surgical treatments that would 1) prevent the occurrence, or 2) reduce the progression rate, or 3) stop/reverse the progression of SARS. The MeSH taxonomy of Medline was used to restrict potential discoveries to selected semantic classes, and to identify potential discoveries efficiently. To enhance the volume of potential discovery, databases were used in addition to Medline. These included the Science Citation Index (SCI) and, in contrast to previous work, a full text database. Because of the richness of the full text, ‘surgical’ queries were developed that targeted the exact types of potential discovery of interest while eliminating clutter more efficiently.

negative: Responding to COVID‐19: How to Navigate a Public Health Emergency Legally and Ethically Few novel or emerging infectious diseases have posed such vital ethical challenges so quickly and dramatically as the novel coronavirus SARS‐CoV‐2. The World Health Organization declared a public health emergency of international concern and recently classified COVID‐19 as a worldwide pandemic. As of this writing, the epidemic has not yet peaked in the United States, but community transmission is widespread. President Trump declared a national emergency as fifty governors declared state emergencies. In the coming weeks, hospitals will become overrun, stretched to their capacities. When the health system becomes stretched beyond capacity, how can we ethically allocate scarce health goods and services? How can we ensure that marginalized populations can access the care they need? What ethical duties do we owe to vulnerable people separated from their families and communities? And how do we ethically and legally balance public health with civil liberties?

negative: Is the spread of COVID-19 across countries influenced by environmental, economic and social factors? The SARS-CoV-2 virus, emerged from Wuhan, China is spreading all over the world in an unprecedented manner, causing millions of infections and thousands of deaths. However, the spread of the disease across countries and regions are not even. Why some countries and regions are more affected than some other countries and regions? We employ simple statistical methods to investigate any linkage between the severity of the disease and the environmental, economic and social factors of countries. The estimation results indicate that the number of confirmed cases of Coronavirus infection is higher in countries with lower yearly average temperatures, higher economic openness, and stronger political democracy. However, findings of this analysis should be interpreted carefully keeping in mind the fact that statistical relations do not necessarily imply causation. Only clinical experiments with medical expertise can confirm how the virus behaves in the environment.

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: CDJ Editorial—What is this Covid-19 crisis?

negative: Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines Dengue is a major public health concern and an economic burden in the Philippines. Despite the country’s improved dengue surveillance, it still suffers from various setbacks and needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of Internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study has two objectives: (1) assess the temporal relationship of weekly GDT and dengue incidence in Metropolitan Manila from 2009–2014; and (2) examine the health-seeking behavior based on dengue-related search queries of the population. The study collated the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the dengue incidence (DI) on a weekly basis for the entire region and annually per city. Data processing of GDT and dengue incidence was performed by conducting an ‘adjustment’ and scaling procedures, respectively, and further analyzed for correlation and cross-correlation analyses using Pearson’s correlation. The relative search volume of the term ‘dengue’ and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google Trends platform. Afterwards, a thematic analysis was employed, and word clouds were generated to examine the health behavior of the population. Results showed that weekly temporal GDT pattern are closely similar to the weekly DI pattern in Metropolitan Manila. Further analysis showed that GDT has a moderate and positive association with DI when adjusted or scaled, respectively. Cross-correlation analysis revealed a delayed effect where GDT leads DI by 1–2 weeks. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito, and (e) other diseases. The majority of the search queries were classified in ‘signs and symptoms’ which indicate the health-seeking behavior of the population towards the disease. Therefore, GDT can be utilized to complement traditional disease surveillance methods combined with other factors that could potentially identify dengue hotspots and help in public health decisions.

negative: Offline: A dangerous virus, but not the one you think

negative: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.

negative: A dynamic modeling tool for estimating healthcare demand from the COVID19 epidemic and evaluating population-wide interventions Objectives. Public health officials need tools to assist with anticipating the healthcare resources required to confront the SARS-COV-2 pandemic. We built a modeling tool to aid practicing public health officials with estimating healthcare demand from the pandemic in their jurisdictions and to evaluate the potential impacts of population-wide social-distancing interventions. Methods. The tool uses a SEIR compartmental model to project the local spread of the pandemic. Users input case counts, healthcare resources, and select intervention strategies to evaluate. Outputs include the number of infections and deaths with and without intervention, and the demand for hospital and critical care beds and ventilators relative to existing capacity. We illustrate the tool using data from three regions of Chile. Results. Our scenarios indicate a surge in COVID-19 patients could overwhelm Chilean hospitals by June, peaking in July or August at 6 to 50 times the current supply of beds and ventilators. A lockdown strategy or combination of case isolation, home quarantine, social distancing of individuals greater than 70 years, and telework interventions may keep treatment demand below capacity. Conclusions. Aggressive interventions can avert substantial morbidity and mortality from COVID-19. Our tool permits rapid evaluation of locally-applicable policy scenarios and updating of results as new data become available.

negative: Projecting the Spread of COVID19 for Germany We model the evolution of the number of individuals that are reported to be sick with COVID-19 in Germany. Our theoretical framework builds on a continuous time Markov chain with four states: healthy without infection, sick, healthy after recovery or after infection but without symptoms and dead. Our quantitative solution matches the number of sick individuals up to the most recent observation and ends with a share of sick individuals following from infection rates and sickness probabilities. We employ this framework to study inter alia the expected peak of the number of sick individuals in a scenario without public regulation of social contacts. We also study the effects of public regulations. For all scenarios we report the expected end of the CoV-2 epidemic. We have four general findings: First, current epidemiological thinking implies that the long-run effects of the epidemic only depend on the aggregate long-run infection rate and on the individual risk to turn sick after an infection. Any measures by individuals and the public therefore only influence the dynamics of spread of CoV-2. Second, predictions about the duration and level of the epidemic must strongly distinguish between the officially reported numbers (Robert Koch Institut, RKI) and actual numbers of sick individuals. Third, given the current (scarce) medical knowledge about long-run infection rate and individual risks to turn sick, any prediction on the length (duration in months) and strength (e.g. maximum numbers of sick individuals on a given day) is subject to a lot of uncertainty. Our predictions therefore offer robustness analyses that provide ranges on how long the epidemic will last and how strong it will be. Fourth, public interventions that are already in place and that are being discussed can lead to more and less severe outcomes of the epidemic. If an intervention takes place too early, the epidemic can actually be stronger than with an intervention that starts later. Interventions should therefore be contingent on current infection rates in regions or countries. Concerning predictions about COVID-19 in Germany, we find that the long-run number of sick individuals (that are reported to the RKI), once the epidemic is over, will lie between 500 thousand and 5 million individuals. While this seems to be an absurdly large range for a precise projection, this reflects the uncertainty about the long-run infection rate in Germany. If we assume that Germany will follow the good scenario of Hubei (and we are even a bit more conservative given discussions about data quality), we will end up with 500 thousand sick individuals over the entire epidemic. If by contrast we believe (as many argue) that once the epidemic is over 70% of the population will have been infected (and thereby immune), we will end up at 5 million cases. Defining the end of the epidemic by less than 100 newly reported sick individuals per day, we find a large variation depending on the effectiveness of governmental pleas and regulations to reduce social contacts. An epidemic that is not influenced by public health measures would end mid June 2020. With public health measures lasting for few weeks, the end is delayed by around one month or two. The advantage of the delay, however, is to reduce the peak number of individuals that are simultaneously sick. When we believe in long-run infection rates of 70%, this number is equally high for all scenarios we went through and well above 1 million. When we can hope for the Hubei-scenario, the maximum number of sick individuals will be around 200 thousand only. Whatever value of the range of long-run infection rates we want to assume, the epidemic will last at least until June, with extensive and potentially future public health measures, it will last until July. In the worst case, it will last until end of August. We emphasize that all projections are subject to uncertainty and permanent monitoring of observed incidences are taken into account to update the projection. The most recent projections are available at https://www.macro.economics.uni-mainz.de/corona-blog/.

negative: Delayed management of Staphyloccocus aureus infective endocarditis in a Middle East respiratory syndrome coronavirus possible case hospitalized in 2015 in Paris, France

negative: The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination. Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.

negative: Dynamic Modeling to Identify Mitigation Strategies for Covid-19 Pandemic Relevant pandemic-spread scenario simulations provide guiding principles for containment and mitigation policy developments. Here we devise a simple model to predict the effectiveness of different mitigation strategies. The model consists of a set of simple differential equations considering the population size, reported and unreported infections, reported and unreported recoveries and the number of Covid-19-inflicted deaths. For simplification, we assume that Covid-19 survivors are immune (e.g. mutations are not considered) and that the virus can only be passed on by persons with undetected infections. While the latter assumption is a simplification (it is neglected that e.g. hospital staff may be infected by detected patients with symptoms), it was introduced here to keep the model as simple as possible. Moreover, the current version of the model does not account for age-dependent differences in the death rates, but considers higher mortality rates due to temporary shortage of intensive care units. Some of the model parameters have been fitted to the reported cases outside of China1 from January 22 to March 12 of the 2020 Covid-19 pandemic. The other parameters were chosen in a plausible range to the best of our knowledge. We compared infection rates, the total number of people getting infected and the number of deaths in six different scenarios. Social distancing or increased testing can contain or drastically reduce the infections and the predicted number of deaths when compared to a situation without mitigation. We find that mass-testing alone and subsequent isolation of detected cases can be an effective mitigation strategy, alone and in combination with social distancing. However, unless one assumes that the virus can be globally defeated by reducing the number of infected persons to zero, testing must be upheld, albeit at reduced intensity, to prevent subsequent waves of infection. The model suggests that testing strategies can be equally effective as social distancing, though at much lower economical costs. We discuss how our mathematical model may help to devise an optimal mix of mitigation strategies against the Covid-19 pandemic. The website corona-lab.ch provides an interactive simulation tool based on the presented model.

negative: The history of respiratory disease management Abstract Over the past 200 years lung diseases have shifted from infections – tuberculosis, pneumonia – to diseases of dirty air – chronic obstructive pulmonary disease, asthma and lung cancer. New diseases have emerged from industrial pollution and HIV infection, while better imaging has revealed others previously unrecognized. Scientific advances in microbiology, imaging and clinical measurement have improved diagnosis and allowed better targeted treatment. Advances in treatment have been dramatic, the most important being drugs (antibiotics, cortisone, β2-adrenoceptor agonists), ventilatory support (from iron lung to nasal positive-pressure ventilation), inhaled therapy (metered dose inhalers, nebulizers) and lung surgery (resections, video-assisted thoracoscopic surgery, transplantation). Delivery of care has shifted from sanatoria for the rich but nothing at all for the poor, to universal coverage in both primary and hospital care. Generalists have turned into super-specialists and doctors have been joined by growing numbers of professions allied to medicine. Management of lung disease has vastly improved but the impact of disease remains.

negative: Which Melbourne metropolitan areas are vulnerable to COVID-19 based on age, disability and access to health services? Using spatial analysis to identify service gaps and inform delivery Abstract Ageing adults (65+) with disability are especially vulnerable to COVID-19 and upon contracting, are a cohort most likely to require palliative care. Therefore, it is very important that health services - particularly health services providing palliative care - are proximately available. Treating the Melbourne metropolitan area as a case-study, a spatial analysis was conducted to clarify priority areas with a significantly high percentage and number of ageing adults (65+) with disability, and high barriers to accessing primary health services. After, travel times from priority areas to (i) palliative medicine, and (ii) hospital services were calculated. The geographic dispersion of areas with people vulnerable to COVID-19 with poor access to palliative care and health services are clarified. Unique methods of health service delivery are required to ensure that vulnerable populations in under-serviced metropolitan areas receive prompt and adequate care. The spatial methodology employed can be implemented in different contexts to support evidence-based COVID-19 and pandemic palliative care service decisions.

negative: Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo Covid-19 data We investigate the transmissibility of coronavirus for symptomatic and asymptomatic patients using the Ningbo Covid-19 data1. Through more in-depth and comprehensive statistical analysis, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients, which is consistent with the original findings in Chen et al.1

negative: Epidemiologie und Kontrollmaßnahmen bei COVID-19 The Coronavirus Disease Pandemic 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2), started in December 2019 in China. SARS-CoV-2 is easily transmitted by droplet infection. After an incubation period of 1–14 days, COVID-19 shows a mild course in 80 % of observed cases and a severe course in 20 %, with a lethality rate of 0.3–5.8 %. Elderly people and people with underlying diseases have a higher risk of severe courses with mandatory ventilation. So far there are neither effective drugs nor vaccinations available, so only public health interventions such as physical distancing and hygiene measures on the one hand and targeted testing followed by isolation and quarantine measures on the other hand are available. China has shown that maximum use of these measures can control the epidemic. The further course and also the consequences for the global economy cannot be clearly predicted at present.

negative: Save the ICU and save lives during the COVID-19 pandemic Appropriate critical care delivery for Coronavirus disease 2019 (COVID-19) is a cornerstone in saving lives. Earlier publications worldwide demonstrate higher mortality among patients receiving mechanical ventilation in intensive care units during “surges” in the number of cases. In contrast, lower mortality outcomes are evident in Japan using CRISIS [CRoss Icu Searchable Information System] data by the national registry, Japan ECMOnet for COVID-19. This highlights the need for scientific analysis of the medical factors contributing to high survival rates and social factors associated with low case “surges,” to gain insight into protective strategies for possible coming waves in the COVID-19 pandemic.

negative: The Three Steps Needed to End the COVID-19 Pandemic: Bold Public Health Leadership, Rapid Innovations, and Courageous Political Will The world is experiencing the expansive spread of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in a global pandemic that is placing strain on health care, economic, and social systems. Commitment to implementing proven public health strategies will require bold public health leadership and courageous acts by politicians. Developing new innovative communication, mitigation, and health care approaches, particularly in the era of social media, is also clearly warranted. We believe that the best public health evidence must inform activities in three priority areas to stop this pandemic: (1) coordinated and consistent stay-at-home orders across multiple jurisdictions, including potential nationwide mandates; (2) rapid scale-up of SARS-CoV-2 testing; and (3) improved health care capacity to respond. This editorial outlines those areas, the rationale behind them, and the call for innovation and engagement of bold public health leadership to empower courageous political action to reduce the number of deaths during this pandemic.

negative: Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Several recognized respiratory viral agents have a neuroinvasive capacity since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Among the various respiratory viruses, coronaviruses are important pathogens of humans and animals. Human Coronaviruses (HCoV) usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly, and immune-compromised individuals, they can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome, or even severe acute respiratory syndrome (SARS). The respiratory involvement of HCoV has been clearly established since the 1960s. In addition, for almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic and could induce an overactivation of the immune system, in part by participating in the activation of autoreactive immune cells that could be associated with autoimmunity in susceptible individuals. Furthermore, it was shown that in the murine CNS, neurons are the main target of infection, which causes these essential cells to undergo degeneration and eventually die by some form of programmed cell death after virus infection. Moreover, it appears that the viral surface glycoprotein (S) represents an important factor in the neurodegenerative process. Given all these properties, it has been suggested that these recognized human respiratory pathogens could be associated with the triggering or the exacerbation of neurological diseases for which the etiology remains unknown or poorly understood.

negative: Resilience resistance: The challenges and implications of urban resilience implementation Growing concern about major threats, including climate change, environmental disasters, and other hazards, is matched with the increased interest and appeal of the concept of urban resilience. Much scholarly attention has focused on how to define urban resilience, in addition to raising questions about its applicability and usefulness. But those debates typically overlook questions of implementation. Implementation is important not only for how cities respond to threats but also because it can influence how urban resilience is perceived, discussed, and understood. The policy literature suggests that implementation is rarely straightforward and has ideological and normative perspectives embedded within it. Building on this literature, this paper argues that urban resilience implementation raises its own conceptual questions for both theory and practice. Further, implementing urban resilience entails its own unique challenges, such as extensive coordination, maintaining adaptability, divergent time horizons, and diverse outcomes. The paper also introduces the idea of resilience resistance as a new challenge for urban resilience. Resistance refers to the condition in which governance systems inherently develop barriers to change, flexibility, and adaptability through implementation. Several aspects of resistance are highlighted, including fatigue, complacency, and overconfidence. However, the implementation process can also have unintended positive effects on a city's capacity to prepare for and respond to shocks.

negative: Chapter 14 The use of host factors in microbial forensics Abstract Advances have been made in the forensic analysis of microbes and toxins. An underdeveloped and underutilized area in microbial forensics is how the host interacts with microorganisms in a way that provides unique signatures for forensic use. For forensic purposes, an immediate goal is to distinguish a potential victim and innocent person from a perpetrator, and to distinguish between a naturally acquired or intentional infection. Principal methods that are sufficiently developed are characterization of the humoral immune response to microbial antigens including vaccine-induced immunity and detection of antibiotics that may be present in a possible perpetrator. This chapter presents central elements of the host response in a simplified fashion and describes a representative example, which, in the appropriate context, has a high potential of providing evidence that may aid an investigation to distinguish a perpetrator from a victim. This chapter also presents information about the immune system so that the interested reader can have a fuller understanding of the immune response in general.

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: Epidemiological and clinical features of 2019-nCoV acute respiratory disease cases in Chongqing municipality, China: a retrospective, descriptive, multiple-center study Background：In January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. Methods：In this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results：267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF-α and INF-γ, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF-α was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). Conclusion:Our study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.

negative: Challenges in RNA virus bioinformatics Motivation: Computer-assisted studies of structure, function and evolution of viruses remains a neglected area of research. The attention of bioinformaticians to this interesting and challenging field is far from commensurate with its medical and biotechnological importance. It is telling that out of >200 talks held at ISMB 2013, the largest international bioinformatics conference, only one presentation explicitly dealt with viruses. In contrast to many broad, established and well-organized bioinformatics communities (e.g. structural genomics, ontologies, next-generation sequencing, expression analysis), research groups focusing on viruses can probably be counted on the fingers of two hands. Results: The purpose of this review is to increase awareness among bioinformatics researchers about the pressing needs and unsolved problems of computational virology. We focus primarily on RNA viruses that pose problems to many standard bioinformatics analyses owing to their compact genome organization, fast mutation rate and low evolutionary conservation. We provide an overview of tools and algorithms for handling viral sequencing data, detecting functionally important RNA structures, classifying viral proteins into families and investigating the origin and evolution of viruses. Contact: manja@uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online. The references for this article can be found in the Supplementary Material.

negative: An urgent call for measures to fight against increasing suicides during COVID-19 pandemic in Nepal

negative: Are we ready for the new fatal Coronavirus: scenario of Pakistan?

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: Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis()

negative: Survival of porcine epidemic diarrhea virus (PEDV) in thermally treated feed ingredients and on surfaces BACKGROUND: Infection with Porcine Epidemic Diarrhea Virus (PEDV) causes vomiting, diarrhea, and dehydration in young pigs. The virus made its first appearance in the U.S. in 2013, where it caused substantial neonatal mortality and economic losses in the U.S. pork industry. Based on outbreak investigations, it is hypothesized that the virus could be transmitted through contaminated feed or contaminated feed surfaces. This potential risk created a demand for research on the inactivation kinetics of PEDV in different environments. Therefore, the objective of this study was to evaluate the survival of PEDV in 9 different feed ingredients when exposed to 60, 70, 80, and 90 °C, as well as the survival on four different surfaces (galvanized steel, stainless steel, aluminum, and plastic). RESULTS: Overall, there were no differences (P > 0.05) in virus survival among the different feed matrices studied when thermally processed at 60 to 90 °C for 5, 10, 15, or 30 min. However, the time necessary to achieve a one log reduction in virus concentration was less (P < 0.05) when ingredients were exposed to temperatures from 70 °C (3.7 min), 80 °C (2.4 min), and 90 °C (2.3 min) compared with 60 °C (4.4 min). The maximum inactivation level (3.9 log) was achieved when heating all ingredients at 90 °C for 30 min. There were no differences in the amount of time necessary to cause a one log reduction in PEDV concentration among the different surfaces. CONCLUSIONS: The results of this study showed that PEDV survival among the 9 feed ingredients evaluated was not different when exposed to thermal treatments for up to 30 min. However, different combinations of temperature and time resulted in achieving a 3 to 4 log reduction of PEDV in all feed ingredients evaluated. Finally, PEDV survival was similar on galvanized steel, stainless steel, aluminum and plastic.

negative: Eosinopenia Phenotype in Patients with Coronavirus Disease 2019: A Multi-center Retrospective Study from Anhui, China Background: Coronavirus disease 19 (COVID-19) has become a global unprecedented pandemic infecting more than one millon people, which is declared by WHO as a international public health emergency. Eosinopenia may predict a poor prognosis of COVID-19. However, to date, there is no detailed analysis of the clinical characteristics of COVID-19 patients with eosinopenia. Research question: The aim of this study was to describe clinical characteristics of COVID-19 patients with eosinopenia. Study Design and Methods: This was a multi-center retrospective study conducted in three tertiary hospitals. A total of 59 patients with COVID-19 were reviewed from January 23, 2020 to March 10, 2020. We described clincial characteristics of patients with COIVD-19 and eosinopenia phenotype. Results: The median age of patients with COVID-19 was 39 years old, and 32 (54,2%) were male. Patients with severe type had higher proportions of dyspnea (50%) and gastrointestinal symptoms (50%) compared with mild or moderate patients. Laboratory findings indicated that lower counts of lymphocyte and eosnophils were observed in patients with severe type. Cough, sputum, and fatigue were more common symptoms in eosinopenia patients compared with non-eosinopenia patients. High proportion of comorbidities was observed in eosinopenia patients. Laboratory findings indicated that lymphocyte counts (median: 101 cells/l ) in eosinopenia patients were significantly less than those of non-eosinopenia patients (median: 167 cells/l, p<0.001). The use of corticosteroids therapy in COVID-19 patients with eosinopenia were notably higher than those in patients with non-eosinopenia (50% vs 13.8%, respectively, p=0.005). Compared with parameters in non-eosinopenia patients, eosinopenia patients were more inclined to have less lymphocyte counts (OR value 6.566, 95%CI[1.101-39.173], p=0.039). Interpretation Eosinopenia are very common in COVID-19 patient, particularly in severe patients. Common symptoms included fever, cough, sputum, and fatigue are frequent in eosinopenia patients. Eosinopenia may represent a novel phenotype in COVID-19, which needs further investigation.

negative: COVID-19 epidemic: Power law spread and flattening of the curve In this paper, we analyze the real-time infection data of COVID-19 epidemic for nine nations. Our analysis is up to 7 April 2020. For China and South Korea, who have already flattened their infection curves, the number of infected individuals (I(t)) exhibits power-law behavior before flattening of the curve. Italy has transitioned to the power-law regime for some time. For the other six nations-USA, Spain, Germany, France, Japan, and India-a power-law regime is beginning to appear after exponential growth. We argue that the transition from an exponential regime to a power-law regime may act as an indicator for flattening of the epidemic curve. We also argue that long-term community transmission and/or the transmission by asymptomatic carriers traveling long distances may be inducing the power-law growth of the epidemic.

negative: Dynamics of COVID-19 outbreak in Poland: an epidemiological analysis of the first two months of the epidemic INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus SARS-CoV-2. OBJECTIVES: Our aim was to present an epidemiological analysis of the first two months (March and April 2020) of the COVID-19 epidemic in Poland. PATIENTS AND METHODS: This analysis was based on data from epidemiological reports collected between March 4 and April 30, 2020, by the Chief Sanitary Inspectorate. These epidemiological reports include data on sociodemographic characteristics of new laboratory-confirmed COVID-19 cases, the number of COVID-19 related deaths, the number of recovered COVID-19 patients, as well as the number of laboratory tests performed. Results: From March 4 to April 30, 2020, a total of 12,877 laboratory-confirmed COVID-19 cases were registered in Poland (55.7% women, mean age 50.6 (20.5) years). The RT-PCR test was performed on 338,000 patients. The notification rate for COVID-19 was 33.2 per 100,000 inhabitants. One-third of laboratory-confirmed COVID-19 cases were among quarantined persons, 26.1% were related to the healthcare system (hospital or clinic), and 13.3% occurred in nursing homes. As of April 30, 2020, 644 COVID-19-related deaths were registered in Poland (46.5% women). The death rate for the whole country was 1.7 per 100,000 inhabitants. CONCLUSIONS: Our data show higher notification rate for COVID-19 among women than men but men more likely to die from COVID-19. The notification rate for COVID-19 in Poland among women aged 45-54 years is two times higher than among men.

negative: Canadian surgery and the events of 2003.

negative: COVID-19 in children: the link in the transmission chain

negative: Diversion of stress granules and P-bodies during viral infection Abstract RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain many translation initiation factors, and processing bodies (P-bodies, PBs), which are enriched for proteins involved in RNA turnover. Because of the inverse relationship between appearance of RNA granules and persistence of translation, many viruses must subvert RNA granule function for replicative purposes. Here we discuss the viruses and mechanisms that manipulate stress granules and P-bodies to promote synthesis of viral proteins. Several themes have emerged for manipulation of RNA granules by viruses: (1) disruption of RNA granules at the mid-phase of infection, (2) prevention of RNA granule assembly throughout infection and (3) co-opting of RNA granule proteins for new or parallel roles in viral reproduction. Viruses must employ one or multiple of these routes for a robust and productive infection to occur. The possible role for RNA granules in promoting innate immune responses poses an additional reason why viruses must counteract the effects of RNA granules for efficient replication.

negative: End-of-life decisions and care in the midst of a global coronavirus (COVID-19) pandemic

negative: Organ function support in patients with coronavirus disease 2019: Tongji experience Coronavirus disease 2019 (COVID-19) is a highly contagious disease and a serious threat to human health. COVID-19 can cause multiple organ dysfunction, such as respiratory and circulatory failure, liver and kidney injury, disseminated intravascular coagulation, and thromboembolism, and even death. The World Health Organization reports that the mortality rate of severe-type COVID-19 is over 50%. Currently, the number of severe cases worldwide has increased rapidly, but the experience in the treatment of infected patients is still limited. Given the lack of specific antiviral drugs, multi-organ function support treatment is important for patients with COVID-19. To improve the cure rate and reduce the mortality of patients with severe- and critical-type COVID-19, this paper summarizes the experience of organ function support in patients with severe- and critical-type COVID-19 in Optical Valley Branch of Tongji Hospital, Wuhan, China. This paper systematically summarizes the procedures of functional support therapies for multiple organs and systems, including respiratory, circulatory, renal, hepatic, and hematological systems, among patients with severe- and critical-type COVID-19. This paper provides a clinical reference and a new strategy for the optimal treatment of COVID-19 worldwide.

negative: Flourishing Being part of, or witnessing, a terrible disaster is clearly very distressing. How do we minimize this kind of distress and continue to flourish in the future as we face extreme climate events such as wildfires and flooding? How do we identify and learn from past events lying hidden, unrecognized and unforeseen as failure incubated? What are the global ‘grand challenges’—both natural and man-made? What are the UN Sustainable Development Goals? To achieve them do we need to reverse the fragmentation of the professions into ‘silos’? What is ‘joined-up’ thinking in ‘joined-up’ organisations and nation states and how important is it? Despite all the advances in science, we know less actually than we think we know. Contingency planning that expects surprises must be the new norm. Learn anew how to learn together is the new wisdom. Use the golden rule ‘do not do to others that you would not have them do to you’, whatever you are told to believe, is our tenet. Behaviour is more important than belief—imperfect doing is better than uncertain knowing. But to do all of this collectively requires leadership that we can trust—perhaps the biggest challenge of all?

negative: Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis Abstract Background An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.

negative: [Covid-19 - deaths and analysis]. Mortality from Covid-19 is monitored in detail and compared between countries with different strategies against the virus. There is, however, often a lack of understanding of what is required in terms of measures and interpretation to enable correct comparisons. The number of deaths from Covid-19 is affected by the testing strategy and many other things that differ between countries. Therefore, today, the most reliable source for monitoring and comparing mortality from Covid-19 is total mortality. In Sweden, there is good correspondence of Covid-19 deaths and total mortality, with a tendency to a higher total mortality indicating some under-reporting of Covid-19 mortality.

negative: A system dynamics approach to understanding the One Health concept There have been many terms used to describe the One Health concept, including movement, strategy, framework, agenda, approach, among others. However, the inter-relationships of the disciplines engaged in the One Health concept have not been well described. To identify and better elucidate the internal feedback mechanisms of One Health, we employed a system dynamics approach. First, a systematic literature review was conducted via searches in PubMed, Web of Knowledge, and ProQuest with the search terms: ‘One Health’ and (concept* or approach*). In addition, we used the HistCite(®) tool to add significant articles on One Health to the library. Then, of the 2368 articles identified, 19 were selected for evaluating the inter-relationships of disciplines engaged in One Health. Herein, we report a visually rich, theoretical model regarding interactions of various disciplines and complex problem descriptors engaged in One Health problem solving. This report provides a conceptual framework for future descriptions of the interdisciplinary engagements involved in One Health.

negative: A pneumonia outbreak associated with a new coronavirus of probable bat origin Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

negative: Sudden Natural Death: Infectious Diseases Abstract A large number of sudden and unexpected deaths are caused by infections. Bacterial and viral infections remain the most common causes of sudden death from infectious diseases. Sudden deaths resulting from infectious causes involving the cardiovascular system are commonly reported due to myocarditis and infective endocarditis while sudden deaths involving the respiratory system are mostly due to pneumonia and tuberculosis. Detailed medicolegal investigation is warranted in sudden deaths due to infectious diseases involving a thorough autopsy and histopathological evaluation along with the use of microbiology and molecular diagnostic methods.

negative: Anosmia and Ageusia: Not an Uncommon Presentation of Covid-19 Infection in Children and Adolescents Since the emergence of a cluster of viral pneumonia cases in Wuhan, Hubei Province, People's Republic of China, at the end of December 2019, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel coronavirus also known as "coronavirus disease 2019 (COVID-19)," as of 7 April 2020, more than 1,214,466 cases of COVID-19 have been reported in more than 200 countries and territories, resulting in more than 67,767 deaths. The disease was recognized by World Health Organization (WHO) as a pandemic on 11 March 2020. Published reports of adult patients with COVID-19 infection described symptoms including fever, cough, fatigue, sputum production, headache, dyspnoea and diarrhoea. Children usually showed milder respiratory symptoms or were asymptomatic, while loss of taste or sensation of smell were seldom reported. In this paper, we report three cases of pediatric patients with COVID-19 infection who presented with anosmia and/or ageusia.

negative: A simple mathematical model for Coronavirus (COVID-19) A novel coronavirus (COVID-19) was identified in Wuhan, China in the end of 2019, it causing an outbreak of viral pneumonia. It caused to the death rate of 4:63% among 571; 678 confirmed cases around the world to the March 28th, 2020. In this brief current study, we will present a simple mathematical model where we show how the probability of successfully getting infected when coming into contact with an infected individual and the per capita contact rate affect the healthy and infected population with time. The proposed model is used to offer predictions about the behavior of COVID-19 for a shorter period of time.

negative: Modulation of Host Cell Death by SARS Coronavirus Proteins Both types of cell death, namely necrosis and apoptosis, are found in organs of SARS coronavirus (CoV) infected patients. The gastrointestinal tract, however, although also a target for SARS-CoV replication, is obviously not affected by cell death mechanisms. Such differences in cell death induction are paralleled by in-vitro studies. In a colon-derived cell line (Caco-2), proapoptotic proteins were down- and antiapoptotic proteins were upregulated during SARS-CoV infection. By contrast, in SARS-CoV infected Vero E6 cells, apoptosis was induced via the p38 MAPK and caspase dependent pathways. Both apoptotic pathways, although mostly the intrinsic signal transduction, can be targeted by structural as well as accessory proteins of SARS-CoV. The fact that all structural and most of the accessory proteins of SARS-CoV are implicated in apoptotic scenarios indicates the fundamental role of apoptosis in the SARS-CoV life cycle. Interestingly, at least for the nucleocapsid protein of SARS-CoV, a cell-type specific manipulation of apoptosis was confirmed.

negative: Urinalysis, but not blood biochemistry, detects the early renal-impairment in patients with COVID-19 Background: In December 2019, a novel coronavirus (SARS-CoV-2) caused infectious disease, termed COVID-19, outbroke in Wuhan, China. COVID-19 patients manifested as lung injury with complications in other organs, such as liver, heart, gastrointestinal tract, especially for severe cases. However, whether COVID-19 causes significant acute kidney injury (AKI) remained controversial. Methods: We retrospectively analyzed the clinical characteristics, urine and blood routine tests and other laboratory parameters of hospitalized COVID-19 patients in Wuhan Union Hospital. Findings: 178 patients, admitted to Wuhan Union hospital from February 02 to February 29, 2020, were included in this study. No patient (0 [0%]) presented increased serum creatinine (Scr), and 5 (2.8%) patients showed increased blood urea nitrogen (BUN), indicating few cases with kidney dysfunction. However, for patients (83) with no history of kidney disease who received routine urine test upon hospitalization, 45 (54.2%) patients displayed abnormality in urinalysis, such as proteinuria, hematuria and leukocyturia, while none of the patients was recorded to have acute kidney injury (AKI) throughout the study. Meanwhile, the patients with abnormal urinalysis usually had worse disease progression reflecting by laboratory parameters presentations, including markers of liver injury, inflammation, and coagulation. Conclusion: Many patients manifested by abnormal urinalysis on admission, including proteinuria or hematuria. Our results revealed that urinalysis is better in unveiling potential kidney impairment of COVID-19 patients than blood chemistry test and urinalysis could be used to reflect and predict the disease severity. We therefore recommend pay more attention in urinalysis and kidney impairment in COVID-19 patients.

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: Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19 Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

negative: Information Diet in Covid-19 Crisis; a Commentary

negative: Gender differences in patients with COVID-19: Focus on severity and mortality Importance: The recent outbreak of Novel Coronavirus (SARS-CoV-2) Disease (COVID-19) has put the world on alert, that is reminiscent of the SARS outbreak seventeen years ago. Objective: We aim to compare the severity and mortality between male and female patients with both COVID-19 and SARS, to explore the most useful prognostic factors for individualized assessment. Design, Setting, and Participants: We extracted the data from a case series of 43 hospitalized patients we treated, a public data set of the first 37 cases died of COVID-19 in Wuhan city and 1019 survived patients from six cities in China. We also analyzed the data of 524 patients with SARS, including 139 deaths, from Beijing city in early 2003. Main Outcomes and Measures: Severity and mortality. Results: Older age and high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. The percentages of older age (≥65 years) were much higher in the deceased group than in the survived group in patients with both COVID-19 (83.8 vs. 13.2, P<0.001) and SARS (37.4 vs. 4.9, P<0.001). In the case series, men tend to be more serious than women (P=0.035), although age was comparable between men and women. In the public data set, age was also comparable between men and women in the deceased group or the survived group in patients with COVID-19. Meanwhile, gender distribution was exactly symmetrical in the 1019 survivors of COVID-19. However, the percentage of male were higher in the deceased group than in the survived group (70.3 vs. 50.0, P=0.015). The gender role in mortality was also observed in SARS patients. Survival analysis showed that men (hazard ratio [95% CI] 1.47 [1.05-2.06, P= 0.025) had a significantly higher mortality rate than women in patients with SARS. Conclusions and Relevance: Older age and male gender are risk factors for worse outcome in patients with COVID. While men and women have the same susceptibility to both SARS-CoV-2 and SARS-CoV, men may be more prone to have higher severity and mortality independent of age and susceptibility.

negative: A Social Network Model of the COVID-19 Pandemic In the COVID-19 coronavirus pandemic, currently vaccines and specific anti-viral treatment are not yet available. Thus, preventing viral transmission by case isolation, quarantine, and social distancing is essential to slowing its spread. Here we model social networks using weighted graphs, where vertices represent individuals and edges represent contact. As public health measures are implemented, connectivity in the graph decreases, resulting in lower effective reproductive numbers, and reduced viral transmission. For COVID-19, model parameters were derived from the coronavirus epidemic in China, validated by epidemic data in Italy, then applied to the United States. We calculate that, in the U.S., the public is able to contain viral transmission by limiting the average number of contacts per person to less than 7 unique individuals over each 5 day period. This increases the average social distance between individuals to 10 degrees of separation.

negative: Robust estimation of diagnostic rate and real incidence of COVID-19 for European policymakers Policymakers need a clear and fast assessment of the real spread of the epidemic of COVID-19 in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths immediately indicate that countries like Italy and Spain have the worst situation as of mid April 2020, on its own, reported cases do not provide a correct picture of the situation. The reason is that different countries diagnose diversely and present very distinctive reported case fatality rate (CFR). The same levels of reported incidence and mortality might hide a very different underlying picture. Here we present a straightforward and robust estimation of the diagnostic rate in each European country. From that estimation we obtain an uniform unbiased incidence of the epidemic. The method to obtain the diagnostic rate is transparent and empiric. The key assumption of the method is that the real CFR in Europe of COVID-19 is not strongly country-dependent. We show that this number is not expected to be biased due to demography nor the way total deaths are reported. The estimation protocol has a dynamic nature, and it has been giving converging numbers for diagnostic rates in all European countries as of mid April 2020. From this diagnostic rate, policy makers can obtain an Effective Potential Growth (EPG) updated everyday providing an unbiased assessment of the countries with more potential to have an uncontrolled situation. The method developed will be used to track possible improvements on the diagnostic rate in European countries as the epidemic evolves.

negative: Investigation of sudden death from Mycobacterium tuberculosis in a foreign-born worker at a resort hotel Abstract A 60 year-old man born in Central America died suddenly in the hallway of his residence on the grounds of a resort hotel where he worked as a dishwasher. The dishwashing station was in a large, poorly ventilated area where a substantial number of food service workers (cooks, wait staff, bus persons, dishwashers, supervisors, etc.) shared air space with the index patient. Several social contacts of the patient reported that he had been coughing for many months before his death. The County Department Of Health conducted a contact investigation, which identified 171 individuals in need of follow-up. Thirty-six percent of those tested in the first round were tuberculin skin test-positive; a second round of testing yielded a 15% (8 of 52) conversion rate.

negative: SARS-CoV-2 (COVID-19): What do we know about children? A systematic review BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.

negative: Community pharmacists and communication in the time of COVID-19: Applying the health belief model Abstract The emergence of the novel coronavirus disease (COVID-19) pandemic presents an unprecedented health communications challenge. Healthcare providers should reinforce behaviors that limit the spread of the pandemic, including social distancing and remaining in the home whenever possible. Formal communications toolkits may not be prepared in a timely fashion. Community pharmacists can reinforce mitigation behaviors by applying the health belief model (HBM). This commentary provides an overview of the HBM and offers suggestions on how community pharmacists can use it as a guide to patient communication in these uncertain contexts.

negative: First human case of avian influenza A (H5N6) in Yunnan province, China OBJECTIVE: To report clinical, virological, and epidemiological features of the first death caused by a H5N6 avian influenza virus in Yunnan Province, China. METHOD: The case was described in clinical expression, chest radiography, blood test and treatment. Real-time RT-PCR was used to detect H5N6 virus RNA in clinical and environment samples. Epidemiological investigation was performed including case exposure history determinant, close contacts follow up, and environment sample collection. RESULTS: The patient initially developed sore throat and coughs on 27 January 2015. The disease progressed to severe pneumonia, multiple organ dysfunction syndrome, and acute respiratory distress syndrome. And the patient died on 6 February. A highly pathogenic avian influenza A H5N6 virus was isolated from the tracheal aspirate specimen of the patient. The viral genome analyses revealed that the H5 hemmagglutinin gene belongs to 2.3.4.4 clade. Epidemiological investigation showed that the patient had exposure to wild bird. All close contacts of the patient did not present the same disease in seven consecutive days. A high H5 positive rate was detected in environmental samples from local live poultry markets. CONCLUSION: The findings suggest that studies on the source of the virus, transmission models, serologic investigations, vaccines, and enhancing surveillance in both humans and birds are necessary.

negative: COVID-19: opportunity arises from a world health crisis

negative: On the possible role of robustness in the evolution of infectious diseases Robustness describes the capacity for a biological system to remain canalized despite perturbation. Genetic robustness affords maintenance of phenotype despite mutational input, necessarily involving the role of epistasis. Environmental robustness is phenotypic constancy in the face of environmental variation, where epistasis may be uninvolved. Here we discuss genetic and environmental robustness, from the standpoint of infectious disease evolution, and suggest that robustness may be a unifying principle for understanding how different disease agents evolve. We focus especially on viruses with RNA genomes due to their importance in the evolution of emerging diseases and as model systems to test robustness theory. We present new data on adaptive constraints for a model RNA virus challenged to evolve in response to UV radiation. We also draw attention to other infectious disease systems where robustness theory may prove useful for bridging evolutionary biology and biomedicine, especially the evolution of antibiotic resistance in bacteria, immune evasion by influenza, and malaria parasite infections.

negative: Isolation of a murine hepatitis virus from Swiss mice treated with antilymphocyte serum In an attempt to transmit feline malignant lymphoma to mice, a murine hepatitis virus (MHV) was accidentally recovered from conventionally reared Swiss mice receiving prolonged treatment with antilymphocyte serum. In these mice, the virus did not require concomitant infection withEperythrozoon coccoides to produce disease. Tests for antibodies against a variety of viruses were performed on serum from control colony mice and mice that recovered from experimental infection as well as on serum pooled from vaccinated and non-vaccinated mice challenged with the recovered agent. Antibodies to the MHV complement fixing (CF) antigen(s) were demonstrated in only the last mentioned serum. Mice harbouring a hepatitis virus may thus be tolerant to their CF antigen(s) in a situation analogous to oncornavirus infection of their natural hosts. The liver pathology was that of a confluent focal-type necrosis resembling that produced by certain other MHV strains. We have labelled this newly isolated virus MHV (Swiss-Cape Town), abbreviated to MHV (S-CT).

negative: Embryonic death in pregnant rats owing to intercurrent infection with Sendai virus and Pasteurella pneumotropica. During an outbreak of Sendai virus infection in a colony of rats used for embryo production, severe lung lesions due to secondary colonization of the rat lungs with Pasteurella pneumotropica were noted. The effect on pregnancy was to cause embryonic death and resorption, leaving a deciduoma with trophoblastic giant cells as the only embryonic remnants. Up to 30% of fetuses in each pregnant animal were affected at the time of severe maternal lung lesions. Heavy growths of Pasteurella pneumotropica were obtained from the lungs of all affected dams. The formation of deciduomas as a result of embryonic death was due to the indirect effect of damage to the lungs during pregnancy rather than the direct pathogenic effect on the developing embryo of the microbial organisms isolated.

negative: The third coronavirus epidemic in the third millennium: what’s next?

negative: Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis

negative: Will Buying Follow Others Ease Their Threat of Death? An Analysis of Consumer Data during the Period of COVID-19 in China How to overcome informational conformity consumer behavior when faced with threats of death is a social problem in response to COVID-19. This research is based on the terror management theory, the need to belong theory and the materialism theory. It uses a theoretical model to determine the relationships between threats of death and informational conformity consumer behavior. From 1453 samples collected during outbreak of COVID-19 in China, we used a structural equation model to test multiple research hypotheses. The result shows that threats of death are positively associated with a need to belong, materialism and informational conformity consumer behavior. The need to belong and materialism can play a mediating role between threats of death and information conformity consumption behavior, and perceived social support can play a moderating role between threats of death and information conformity consumption behavior.

negative: Psychopathological symptoms during Covid-19 quarantine in spanish general population: a preliminary analysis based on sociodemographic and occupational-contextual factors./ Sintomas psicopatologicos durante la cuarentena por Covid-19 en poblacion gen OBJECTIVE: Coronavirus (COVID-19) pandemic disease forced different countries to adopt quarantine measures These actions could have an impact on mental health in the general population The objective of this study was to analyze the differences in psychopathological symptoms shown by Spanish general population during the COVID-19 quarantine based on sociodemographic, occupational and environmental-contextual variables METHODS: A cross-sectional pilot study was performed in a sample of 151 participants aged between 18-76 years old The Symptom Assessment-45 Questionnaire via online was used to measure the severity of psychopathology symptoms Socio-demographic, environmental and occupational variables were collected with an ad hoc questionnaire The data were gathered from the 3rd to the 6th of April, 2020 A descriptive and comparative analysis was carried out using parametric contrasts (t test and ANOVA) RESULTS: The younger participants (18-35 years) showed higher levels of hostility (t=2 24;p=0 02), depression (t=2 56;p=0 01), anxiety (t=2 78;p=0 006) and interpersonal sensitivity (t=2 08;p=0 04) than older participants (36-76 years) The active or employed people presented lower values of depressive symptoms (t=2 10;p=0 04) than unemployed people The participants who dedicate less than 30 minutes on getting informed about COVID-19 showed higher scores for hostility (t=2 36;p=0 02) and interpersonal sensitivity (t=1 98;p=0 04) than participants who indicated dedicating at least 30 minutes People who played sport daily reported a lower level of somatization symptoms (t=-2 11;p=0 03) than persons that did not play sport Those who had relatives, acquaintances, etc with COVID-19 reported higher levels of anxiety (t=2 09;p=0 04) than those who did not have close people infected Lastly, participants who lived alone showed a higher level of psychoticism (F=3 93;p=0 02) compared to those who lived with more than two people CONCLUSIONS: The findings of this study show that during quarantine can be identified groups with higher psychological vulnerability based on sociodemographic and occupational-contextual factors OBJETIVO: La enfermedad pandemica por coronavirus (COVID-19) ha hecho necesaria la adopcion de medidas de cuarentena en diferentes paises Estas medidas podrian tener un impacto sobre la salud mental de la poblacion general en confinamiento El objetivo del trabajo fue analizar las diferencias en la sintomatologia psicopatologica mostrada por la poblacion general espanola durante la cuarentena por COVID-19 en funcion de variables sociodemograficas, ambientales y ocupacionales METODOS: Se realizo un estudio trasversal en una muestra de 151 participantes, con edades comprendidas entre los 18 y los 76 anos, en el que se utilizo de forma online la version espanola del Symptom Assessment-45 Questionnaire para medir el nivel de sintomas psicopatologicos Se recogieron tambien variables sociodemograficas, ambientales y de ocupacion (mediante una encuesta ad hoc) La informacion fue recogida del 3 al 6 abril de 2020 Se realizo un analisis descriptivo y comparativo utilizando contrastes parametricos (prueba t y ANOVA) RESULTADOS: Los participantes mas jovenes (18-35 anos) mostraron niveles mas altos de hostilidad (t=2,24;p=0,02), depresion (t=2,56;p=0,01), ansiedad (t=2,78;p=0,006) y sensibilidad interpersonal (t=2,08;p=0,04) que los participantes mayores (36-76 anos) Las personas activas o empleadas presentaron valores mas bajos de sintomas depresivos (t=2,10;p=0,04) que las personas desempleadas Los participantes que dedicaron menos de 30 minutos a informarse sobre el COVID-19 mostraron puntuaciones mas altas en hostilidad (t=2,36;p=0,02) y sensibilidad interpersonal (t=1,98;p=0,04) que los participantes que indicaron dedicar al menos 30 minutos Las personas que practicaban deporte diariamente informaron de un menor nivel de sintomas de somatizacion (t=-2,11;p=0,03) que las personas que no practicaban deporte Aquellos que tenian familiares, conocidos, etc con COVID-19 informaron de niveles mas altos de ansiedad (t=2,09;p=0,04) que aquellos que no tenian a personas cercanas infectadas Por ultimo, los participantes que vivian solos mostraron un mayor nivel de psicoticismo (F=3,93;p=0,02) en comparacion con aquellos que vivian con mas de dos personas CONCLUSIONES: Los resultados de este estudio muestran que durante la cuarentena se pueden identificar grupos con mayor vulnerabilidad psicologica en funcion de factores sociodemograficos y ocupacionales-contextuales

negative: Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter–defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.

negative: An Overview of the Most Significant Zoonotic Viral Pathogens Transmitted from Animal to Human in Saudi Arabia Currently, there has been an increasing socioeconomic impact of zoonotic pathogens transmitted from animals to humans worldwide. Recently, in the Arabian Peninsula, including in Saudi Arabia, epidemiological data indicated an actual increase in the number of emerging and/or reemerging cases of several viral zoonotic diseases. Data presented in this review are very relevant because Saudi Arabia is considered the largest country in the Peninsula. We believe that zoonotic pathogens in Saudi Arabia remain an important public health problem; however, more than 10 million Muslim pilgrims from around 184 Islamic countries arrive yearly at Makkah for the Hajj season and/or for the Umrah. Therefore, for health reasons, several countries recommend vaccinations for various zoonotic diseases among preventive protocols that should be complied with before traveling to Saudi Arabia. However, there is a shortage of epidemiological data focusing on the emerging and reemerging of zoonotic pathogens transmitted from animal to humans in different densely populated cities and/or localities in Saudi Arabia. Therefore, further efforts might be needed to control the increasing impacts of zoonotic viral disease. Also, there is a need for a high collaboration to enhance the detection and determination of the prevalence, diagnosis, control, and prevention as well as intervention and reduction in outbreaks of these diseases in Saudi Arabia, particularly those from other countries. Persons in the health field including physicians and veterinarians, pet owners, pet store owners, exporters, border guards, and people involved in businesses related to animal products have adopted various preventive strategies. Some of these measures might pave the way to highly successful prevention and control results on the different transmission routes of these viral zoonotic diseases from or to Saudi Arabia. Moreover, the prevention of these viral pathogens depends on socioeconomic impacts, available data, improved diagnosis, and highly effective therapeutics or prophylaxis.

negative: Estimating weekly excess mortality at subnational level in Italy during the COVID-19 pandemic Background Excess mortality from all-cause has been estimated at national level for different countries, to provide a picture of the total burden of the COVID-19 pandemic. Nevertheless, there have been no attempts at modelling it at high spatial resolution, needed to understand geographical differences in the mortality patterns, to evaluate temporal lags and to plan for future waves of the pandemic. Methods This is the first subnational study on excess mortality during the COVID-19 pandemic in Italy, the third most-hit country. We considered municipality level and estimated all-cause mortality weekly trends based on the first four months of 2016 -- 2019. We specified a Bayesian hierarchical model allowing for spatial heterogeneity as well as for non-linear smooth spatio-temporal terms. We predicted the weekly mortality rates at municipality level for 2020 based on the modelled spatio-temporal trends (i.e.~in the absence of the pandemic) and estimated the excess mortality and the uncertainty surrounding it. Results We found strong evidence of excess mortality for Northern Italy, with higher mortality rates than expected from the end of February in Lombardia, with total excess deaths of 23,946 (23,013 -- 24,786), and the beginning of March for North East and North West with total excess deaths of 8,033 (7,061 -- 9,044) and 1,588 (404 -- 2,700) respectively. We found marked geographical differences, with percent excess of up to 88.9% (81.9% -- 95.2%) at the peak of the pandemic, in the city of Bergamo (Lombardia).

negative: Pathogens, prejudice, and politics: the role of the global health community in the European refugee crisis Summary Involuntary migration is a crucially important global challenge from an economic, social, and public health perspective. The number of displaced people reached an unprecedented level in 2015, at a total of 60 million worldwide, with more than 1 million crossing into Europe in the past year alone. Migrants and refugees are often perceived to carry a higher load of infectious diseases, despite no systematic association. We propose three important contributions that the global health community can make to help address infectious disease risks and global health inequalities worldwide, with a particular focus on the refugee crisis in Europe. First, policy decisions should be based on a sound evidence base regarding health risks and burdens to health systems, rather than prejudice or unfounded fears. Second, for incoming refugees, we must focus on building inclusive, cost-effective health services to promote collective health security. Finally, alongside protracted conflicts, widening of health and socioeconomic inequalities between high-income and lower-income countries should be acknowledged as major drivers for the global refugee crisis, and fully considered in planning long-term solutions.

negative: Prediction of repurposed drugs for treating lung injury in COVID-19 Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Inhibition of Angiotensin-converting enzyme 2 (ACE2) caused by spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value<0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues, including signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA. It also uniquely targets genes related to lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.

negative: A model for COVID-19 prediction in Iran based on China parameters Background: The rapid spread of COVID-19 virus from China to other countries and outbreaks of disease require an epidemiological analysis of the disease in the shortest time and an increased awareness of effective interventions. The purpose of this study was to estimate the COVID-19 epidemic in Iran based on the SIR model. The results of the analysis of the epidemiological data of Iran from January 22 to March 8, 2020 were investigated and the prediction was made until March 29, 2020. Methods: By estimating the three parameters of time-dependent transmission rate, time-dependent recovery rate, and time-dependent mortality rate from Covid-19 outbreak in China, and using the number of Covid-19 infections in Iran, we predicted the number of patients for the next month in Iran. Each of these parameters was estimated using GAM models. All analyses were conducted in R software using the mgcv package. Findings: On average, 925 people with COVID-19 are expected to be infected daily in Iran. The epidemic peaks within one week (15.03.2020 to 03.21.2020) and reaches its highest point on 03.18.2020 with 1126 infected cases. Conclusion: The most important point is to emphasize the timing of the epidemic peak, hospital readiness, government measures and public readiness to reduce social contact.

negative: Human Coronavirus-HKU1 Infection Among Adults in Cleveland, Ohio BACKGROUND. Human coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness. Coronavirus-HKU1 has been described predominantly among children less than 5 years of age in the United States with few studies characterizing the disease spectrum among adults. METHODS. Nasopharyngeal specimens of patients with respiratory symptoms were analyzed for CoV-HKU1 by NxTAG Respiratory Pathogen Panel multiplex assay from February 7, 2016 to April 30, 2016. Epidemiologic, clinical, and laboratory data were collected on adults (patients >18 years) whose samples screened positive. RESULTS. Of 832 adult respiratory specimens screened, 13 (1.6%) cases of CoV-HKU1 were identified. Adults age ranged between 23 and 75 years and 6 (46%) were males. All of whom had 1 or more respiratory symptoms, and 5 (38%) also reported 1 or more gastrointestinal symptoms. Eleven (85%) reported history of smoking and 5 (38%) used inhaled steroids. Seven (54%) required hospitalization, 5 (71%) of these needed supplemental oxygen, and 2 (29%) were admitted to intensive care. Median length of hospitalization was 5 days. Eight (62%) received antibiotics despite identification of CoV-HKU1. Infectious work-up in 1 patient who died did not reveal any other pathogen. In 2 (15%) CoV-HKU1-positive adults, the only viral coinfection detected was influenza A. CONCLUSIONS. Coronavirus-HKU1 accounted for 1.6% of adult respiratory infections and should be considered in differential diagnosis of severe respiratory illnesses among adults.

negative: Assessing Differential Impacts of COVID-19 on Black Communities Purpose Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.

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: Wastewater-Based Epidemiology for Early Detection of Viral Outbreaks The immense global burden of infectious disease outbreaks and the need to establish prediction and prevention systems have been recognized by the World Health Organization (WHO), the National Institutes of Health (NIH), the United States Agency of International Development (USAID), the Bill and Melinda Gates Foundation, and the international scientific community. Despite multiple efforts, this infectious burden is still increasing. For example, it has been reported that between 1.5 and 12 million people die each year from waterborne diseases and diarrheal diseases are listed within the top 15 leading causes of death worldwide. Rapid population growth, climate change, natural disasters, immigration, globalization, and the corresponding sanitation and waste management challenges are expected to intensify the problem in the years to come.

negative: Ontology-Based Approach to Social Data Sentiment Analysis: Detection of Adolescent Depression Signals BACKGROUND: Social networking services (SNSs) contain abundant information about the feelings, thoughts, interests, and patterns of behavior of adolescents that can be obtained by analyzing SNS postings. An ontology that expresses the shared concepts and their relationships in a specific field could be used as a semantic framework for social media data analytics. OBJECTIVE: The aim of this study was to refine an adolescent depression ontology and terminology as a framework for analyzing social media data and to evaluate description logics between classes and the applicability of this ontology to sentiment analysis. METHODS: The domain and scope of the ontology were defined using competency questions. The concepts constituting the ontology and terminology were collected from clinical practice guidelines, the literature, and social media postings on adolescent depression. Class concepts, their hierarchy, and the relationships among class concepts were defined. An internal structure of the ontology was designed using the entity-attribute-value (EAV) triplet data model, and superclasses of the ontology were aligned with the upper ontology. Description logics between classes were evaluated by mapping concepts extracted from the answers to frequently asked questions (FAQs) onto the ontology concepts derived from description logic queries. The applicability of the ontology was validated by examining the representability of 1358 sentiment phrases using the ontology EAV model and conducting sentiment analyses of social media data using ontology class concepts. RESULTS: We developed an adolescent depression ontology that comprised 443 classes and 60 relationships among the classes; the terminology comprised 1682 synonyms of the 443 classes. In the description logics test, no error in relationships between classes was found, and about 89% (55/62) of the concepts cited in the answers to FAQs mapped onto the ontology class. Regarding applicability, the EAV triplet models of the ontology class represented about 91.4% of the sentiment phrases included in the sentiment dictionary. In the sentiment analyses, “academic stresses” and “suicide” contributed negatively to the sentiment of adolescent depression. CONCLUSIONS: The ontology and terminology developed in this study provide a semantic foundation for analyzing social media data on adolescent depression. To be useful in social media data analysis, the ontology, especially the terminology, needs to be updated constantly to reflect rapidly changing terms used by adolescents in social media postings. In addition, more attributes and value sets reflecting depression-related sentiments should be added to the ontology.

negative: Estimating the risk of COVID-19 death during the course of the outbreak in Korea, February-March, 2020 Background: In Korea, a total of 8,799 confirmed cases of COVID-19 including 102 deaths have been recorded as of Mar 21, 2020. The time-delay adjusted case fatality risk of COVID-19 in Korea is yet to be estimated. Methods: We obtained the daily series of confirmed cases and deaths in Korea reported prior to March 21,2020. Using statistical methods, we estimated the time-delay adjusted risk for death from COVID-19 in the city of Daegu, Gyeongsangbuk-do, other regions in Korea, as well as for the entire country. Results: Our model-based crude CFR fitted the observed data well throughout the course of the epidemic except for the very early stage in Gyeongsangbuk-do, partially due to the reporting delay. Our estimates of the risk for death in Gyeongsangbuk-do reached 2.4% (95% CrI: 1.6-3.4%), 1.3% (95% CrI: 1.0-1.6%) in Daegu and 0.7% (95% CrI: 0.3-1.4%) in other regions, whereas the national estimate of the risk for death was estimated at 1.4% (95% CrI: 1.2-1.7%) in Korea. Conclusions: The relatively low CFRs are associated with the early implementation of public health interventions including widespread testing, social distancing, and delayed school openings in Korea. Geographic differences in CFR are likely influenced by clusters of nosocomial transmission.

negative: Properties of a coronavirus isolated from a cow with epizootic diarrhea Abstract A coronavirus (Kakegawa isolate) isolated from a cow with epizootic diarrhea was grown in BEK-1 cells and examined for biophysical and biochemical properties. The Kakegawa isolate was able to replicate in the presence or absence of 5-iodo-2′-deoxy-uridine, indicating that its viral nucleic acid was RNA. It was highly sensitive to ether and chloroform, and moderately sensitive to trypsin and heat. It was, however, readily stabilized by treatment with cation at 50°C for 1 h. Its infectivity was slightly reduced at pH 3.0. The virus passed through a membrane filter of 200 nm pore size, but not through one of 100 nm pore size. The buoyant density of the virus was determined in a sucrose density gradient. The peak of infectivity and hemagglutinin activity was found at a density of 1.182. Neutralization and hemagglutination inhibition tests showed a close serological relationship between the Kakegawa isolate and the American strain of calf diarrhea coronavirus.

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: Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1—the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (−.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also −.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.

negative: SARS-CoV-2 detection from nasopharyngeal swab samples without RNA extraction The ongoing COVID-19 pandemic has reached more than 200 countries and territories worldwide. Given the large requirement of SARS-CoV-2 diagnosis and considering that RNA extraction kits are in short supply, we investigated whether two commercial RT-qPCR kits were compatible with direct SARS-CoV-2 detection from nasopharyngeal swab samples. We show that one of the tested kits is fully compatible with direct SARS-CoV-2 detection suggesting that omission of an RNA extraction step should be considered in SARS-CoV-2 diagnosis.

negative: The effects of SNS communication: How expressing and receiving information predict MERS-preventive behavioral intentions in South Korea Abstract Individuals use social network sites (SNSs) as an effective tool for communicating relevant information with others during the outbreak of infectious diseases. However, little is known about the underlying mechanism through which communicative behaviors influence preventive behaviors. Thus, in the context of Middle East respiratory syndrome (MERS) in South Korea, this study investigated how two communicative behaviors (message expression and reception) in SNSs affected the communicators’ intentions to engage in MERS-preventive behaviors. Using data collected from a nationally representative panel survey of 1000 Korean adults aged 19 or older, we examined a theoretical expression and reception effects model. Results support the presence of effects from expressing and receiving MERS-related information via SNSs and their underlying mechanism during South Korea’s MERS outbreak. Public health officials and communication professionals should actively use SNS communication in coping with public health crisis caused by emerging infectious diseases.

negative: Complement pathway amplifies caspase-11–dependent cell death and endotoxin-induced sepsis severity Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel mediators of caspase-11–dependent cell death. We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death. Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling. We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice. We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis. Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.

negative: Preparedness and Preventive Behaviors for a Pandemic Disaster Caused by COVID-19 in Serbia Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The disease was first detected in Wuhan, the capital of China's Hubei province, in December 2019 and has since spread globally, especially to Europe and North America, resulting in the ongoing global coronavirus pandemic disaster of 2019-2020. Although most cases have mild symptoms, there is some progression to viral pneumonia and multi-organ failure and death. More than 4.6 million cases have been registered across 216 countries and territories as of 19 April 2020, resulting in more than 311,000 deaths. Risk to communities with continued widespread disease transmission depends on characteristics of the virus, including how well it spreads between people; the severity of resulting illness; and the medical or other measures available to control the impact of the virus (for example, vaccines or medications that can treat the illness) and the relative success of these. In the absence of vaccines or medications, non-pharmaceutical interventions were the most important response strategy based on community interventions such as person-to-person distancing, mask-wearing, isolation and good personal hygiene (hand-washing)-all of which have been demonstrated can reduce the impact of this seemingly unstoppable globally spreading natural disaster. This paper presents the results of quantitative research regarding the level of citizen preparedness for disasters caused by coronavirus disease (COVID-19) in Serbia. The survey was conducted using a questionnaire that was requested and then collected online among 975 respondents during disaster in April 2020. The questionnaire examined citizens' basic socio-economic and demographic characteristics, their knowledge, preparedness, risk perception and preventive measures taken individually and as a community to prevent the death and widespread transmission of novel coronavirus disease 2019 in the Republic of Serbia. Based on the findings that there are major differences in the public's perception of risks posed by communicable disease threats such as presented by COVID-19, emergency management agencies should use these differences to develop targeted strategies to enhance community and national preparedness by promoting behavioral change and improving risk management decision-making.

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: A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world(1,2,3). A new coronavirus (SARS-CoV) was identified as the SARS pathogen(4,5,6,7), which triggered severe pneumonia and acute, often lethal, lung failure(8). Moreover, among infected individuals influenza such as the Spanish flu(9,10) and the emergence of new respiratory disease viruses(11,12) have caused high lethality resulting from acute lung failure(13). In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor(14). The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users.

negative: Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis Background: Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarised the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers. Methods: We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Study quality was assessed using a modified version of the Newcastle Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI). Results: In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 6.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%. Conclusion: Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

negative: SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized.

negative: COVID-19 (Coronavirus Disease-19): Traditionelle Chinesische Medizin einschließlich Akupunktur zur Linderung — Ein Bericht aus Wuhan, Hubei Provinz in China

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: The infection fatality rate of COVID-19 inferred from seroprevalence data Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of May 12, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Results Twelve studies were identified with usable data to enter into calculations. Seroprevalence estimates ranged from 0.113% to 25.9% and adjusted seroprevalence estimates ranged from 0.309% to 33%. Infection fatality rates ranged from 0.03% to 0.50% and corrected values ranged from 0.02% to 0.40%. Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

negative: Single-cell analysis of severe COVID-19 patients reveals a monocyte-driven inflammatory storm attenuated by Tocilizumab Despite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.

negative: Data-driven modeling reveals a universal dynamic underlying the COVID-19 pandemic under social distancing We show that the COVID-19 pandemic under social distancing exhibits universal dynamics. The cumulative numbers of both infections and deaths quickly cross over from exponential growth at early times to a longer period of power law growth, before eventually slowing. In agreement with a recent statistical forecasting model by the IHME, we show that this dynamics is well described by the erf function. Using this functional form, we perform a data collapse across countries and US states with very different population characteristics and social distancing policies, confirming the universal behavior of the COVID-19 outbreak. We show that the predictive power of statistical models is limited until a few days before curves flatten, forecast deaths and infections assuming current policies continue and compare our predictions to the IHME models. We present simulations showing this universal dynamics is consistent with disease transmission on scale-free networks and random networks with non-Markovian transmission dynamics.

negative: In der Pandemie: Wo sind all die Herzinfarkte geblieben? Berichte über besorgniserregende Rückgänge bei den Klinikaufnahmen von Patienten mit akutem Herzinfarkt nehmen in der COVID-19-Pandemie zu.

negative: What Can We Estimate from Fatality and Infectious Case Data using the Susceptible-Infected-Removed (SIR) model? A case Study of Covid-19 Pandemic The rapidly spreading Covid-19 that affected almost all countries, was first reported at the end of 2019. As a consequence of its highly infectious nature, countries all over the world have imposed extremely strict measures to control its spread. Since the earliest stages of this major pandemic, academics have done a huge amount of research in order to understand the disease, develop medication, vaccines and tests, and model its spread. Among these studies, a great deal of effort has been invested in the estimation of epidemic parameters in the early stage, for the countries affected by Covid-19, hence to predict the course of the epidemic but the variability of the controls over the course of the epidemic complicated the modeling processes. In this article, the determination of the basic reproduction number, the mean duration of the infectious period, the estimation of the timing of the peak of the epidemic wave is discussed using early phase data. Daily case reports and daily fatalities for ten countries over the period January 22, 2020 - April 18, 2020 are evaluated using the Susceptible-Infected-Removed (SIR) model. For each country, the SIR models fitting cumulative infective case data within 5% error are analysed. It is observed that the basic reproduction number and the mean duration of the infectious period can be estimated only in cases where the spread of the epidemic is over (for China and South Korea in the present case). Nevertheless, it is shown that the timing of the maximum and timings of the inflection points of the proportion of infected individuals can be robustly estimated from the normalized data. The validation of the estimates by comparing the predictions with actual data has shown that the predictions were realised for all countries except USA, as long as lock-down measures were retained.

negative: Mapping the changing Internet attention to the spread of coronavirus disease 2019 in China The incessant spread of the coronavirus disease 2019 (COVID-19) has been a great threat to human health. By 17 March 2020, the number of laboratory-confirmed cases had exceeded 179,000, with more than 7000 deaths across at least 150 countries. Due to the extremely contagious nature of COVID-19, the Chinese government has made broad and aggressive responses to restrict movement, transportation, and business for six to eleven weeks. Wuhan, a city in Hubei province from which COVID-19 emanated, has been quarantined since 12 January 2020, and many other cities have been placed under travel restrictions. Citizens have been strongly encouraged to stay home and limit face-to-face contact; as a result, people’s daily lives are dominated by the Internet as never before. Here, we visualize the spread of COVID-19 and people’s Internet attention in China in the form of cartograms using the diffusion-based method.

negative: COVID-19: Disease, management, treatment, and social impact Abstract COVID-19 was originated from Wuhan city of Hubei Province in China in December 2019. Since then it has spread in more than 210 countries and territories. It is a viral disease due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. The patients show flu-like symptoms with a dry cough, sore throat, high fever, and breathing problems. The disease due to SARS-CoV-2 was named as COVID-19. About 2.2 million people have been infected with more than 0.15 million deaths globally. The United States of America is the most affected country with the highest patients of about 0.7 million. Despite great efforts, there is no treatment of this disease. However, prevention and management are the best options. This article describes SARS-CoV-2, disease, prevention and management, treatment and social impact on society. It was analyzed that a combination of antiviral drugs with hydroxyl-chloroquine and azithromycin (with the consultation of a medical practitioner) may be the best option to treat the patients, depending on the patient's conditions and symptoms. However, Unani therapy may be useful along with allopathic treatment. It is urgently advised and requested that all the persons should follow the preventive measures, managements and quarantine strictly without any religious discrepancy otherwise the situation may be the worst. Also, there is an urgent requirement to educate our new generation for science and technology to fight against any such disaster in future; if any. There is no need to be panic and proper prevention and management are essential to combat this disease. This article may be useful to create awareness among the public, to prevent, manage and treat COVID-19.

negative: The Data set for Patient Information Based Algorithm to Predict Mortality Cause by COVID-19 Abstract The data of COVID-19 disease in China and then in South Korea were collected daily from several different official websites. The collected data included 33 death cases in Wuhan city of Hubei province during early outbreak as well as confirmed cases and death toll in some specific regions, which were chosen as representatives from the perspective of the coronavirus outbreak in China. Data were copied and pasted onto Excel spreadsheets to perform data analysis. A new methodology, Patient Information Based Algorithm (PIBA) [1], has been adapted to process the data and used to estimate the death rate of COVID-19 in real-time. Assumption is that the number of days from inpatients to death fall into a pattern of normal distribution and the scores in normal distribution can be obtained by observing 33 death cases and analysing the data [2]. We selected 5 scores in normal distribution of these durations as lagging days, which will be used in the following estimation of death rate. We calculated each death rate on accumulative confirmed cases with each lagging day from the current data and then weighted every death rate with its corresponding possibility to obtain the total death rate on each day. While the trendline of these death rate curves meet the curve of current ratio between accumulative death cases and confirmed cases at some points in the near future, we considered that these intersections are within the range of real death rates. Six tables were presented to illustrate the PIBA method using data from China and South Korea. One figure on estimated rate of infection and patients in serious condition and retrospective estimation of initially occurring time of CORID-19 based on PIBA.

negative: Understanding the asymmetric spread and case fatality rate (CFR) for COVID-19 among countries The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are rising rapidly every day in the world, causing the disease COVID-19 with around 2 million people infected and more than 100,000 people died so far, in more than 200 countries. One of the baffling aspects of this pandemic is the asymmetric increase in cases and case fatality rate (CFR) among countries. We analyze the time series of the infection and fatality numbers and found two interesting aspects. Firstly, the rate of spread in a region is directly connected to the population density of the region where the virus is spreading. For example, the high rate of increase in cases in the United States of America (USA) is related to the high population density of New York City. This is shown by scaling the cumulative number of cases with a measure of the population density of the affected region in countries such as Italy, Spain, Germany, and the USA and we see that the curves are coinciding. Secondly, we analyzed the CFR number as a function of the number of days, since the first death, and we found that there are two clear categories among countries: one category with high CFR numbers (around 10%) and the other category with low CFR numbers (2% to 4%). When we analyzed the results, we see that countries with lower CFR numbers more or less tend to have implemented active control measures such as aggressive testing, tracking down possible infections, effective quarantine measures, etc. Moreover, we did not see any convincing correlation between mortality rates and the median age of the population.

negative: Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. In-depth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine.

negative: The Framework for the Prediction of the Critical Turning Period for Outbreak of COVID-19 Spread in China based on the iSEIR Model The goal of this study is to establish a general framework for predicting the so-called critical Turning Period in an infectious disease epidemic such as the COVID-19 outbreak in China early this year. This framework enabled a timely prediction of the turning period when applied to Wuhan COVID-19 epidemic and informed the relevant authority for taking appropriate and timely actions to control the epidemic. It is expected to provide insightful information on turning period for the world's current battle against the COVID-19 pandemic. The underlying mathematical model in our framework is the individual Susceptible-Exposed-Infective-Removed (iSEIR) model, which is a set of differential equations extending the classic SEIR model. We used the observed daily cases of COVID-19 in Wuhan from February 6 to 10, 2020 as the input to the iSEIR model and were able to generate the trajectory of COVID-19 cases dynamics for the following days at midnight of February 10 based on the updated model, from which we predicted that the turning period of CIVID-19 outbreak in Wuhan would arrive within one week after February 14. This prediction turned to be timely and accurate, providing adequate time for the government, hospitals, essential industry sectors and services to meet peak demands and to prepare aftermath planning. Our study also supports the observed effectiveness on flatting the epidemic curve by decisively imposing the Lockdown and Isolation Control Program in Wuhan since January 23, 2020. The Wuhan experience provides an exemplary lesson for the whole world to learn in combating COVID-19.

negative: Infectious disease. Combating emerging viral threats.

negative: Potential and challenges of tannins as an alternative to in-feed antibiotics for farm animal production Naturally occurring plant compounds including tannins, saponins and essential oils are extensively assessed as natural alternatives to in-feed antibiotics. Tannins are a group of polyphenolic compounds that are widely present in plant region and possess various biological activities including antimicrobial, anti-parasitic, anti-viral, antioxidant, anti-inflammatory, immunomodulation, etc. Therefore, tannins are the major research subject in developing natural alternative to in-feed antibiotics. Strong protein affinity is the well-recognized property of plant tannins, which has successfully been applied to ruminant nutrition to decrease protein degradation in the rumen, and thereby improve protein utilization and animal production efficiency. Incorporations of tannin-containing forage in ruminant diets to control animal pasture bloat, intestinal parasite and pathogenic bacteria load are another 3 important applications of tannins in ruminant animals. Tannins have traditionally been regarded as “anti-nutritional factor” for monogastric animals and poultry, but recent researches have revealed some of them, when applied in appropriate manner, improved intestinal microbial ecosystem, enhanced gut health and hence increased productive performance. The applicability of plant tannins as an alternative to in-feed antibiotics depends on many factors that contribute to the great variability in their observed efficacies.

negative: Teicoplanin potently blocks the cell entry of 2019-nCoV Since December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.

negative: Q&A: The novel coronavirus outbreak causing COVID-19

negative: Novel astroviruses in insectivorous bats. Bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. They are the reservoir of a number of human zoonotic diseases including Nipah, Ebola, and severe acute respiratory syndrome. We report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in Hong Kong, in particular, bats belonging to the genera Miniopterus and Myotis. Astroviruses are important causes of diarrhea in many animal species, including humans. Many of the bat astroviruses form distinct phylogenetic clusters in the genus Mamastrovirus within the family Astroviridae. Virus detection rates of 36% to 100% and 50% to 70% were found in Miniopterus magnater and Miniopterus pusillus bats, respectively, captured within a single bat habitat during four consecutive visits spanning 1 year. There was high genetic diversity of viruses in bats found within this single habitat. Some bat astroviruses may be phylogenetically related to human astroviruses, and further studies with a wider range of bat species in different geographic locations are warranted. These findings are likely to provide new insights into the ecology and evolution of astroviruses and reinforce the role of bats as a reservoir of viruses with potential to pose a zoonotic threat to human health.

negative: Failing our Most Vulnerable: COVID-19 and Long-Term Care Facilities in Ontario Background: The COVID-19 epidemic has taken a fearsome toll on individuals residing in long-term care facilities (LTC). As of April 10, 2020 half COVID-19 deaths in Canada had occurred in LTC. We sought to better understand trends and risk factors for COVID-19 death in LTC in Ontario. Methods: We analyzed a COVID-19 outbreak database created by the Ontario Ministry of Health, for the period March 29-April 7, 2020. Mortality incidence rate ratios for LTC were calculated with community living Ontarians aged > 69 used as the comparator group. Count-based regression methods were used to model temporal trends and identify associations between infection risk in staff and residents, and subsequent LTC resident death. Results: Confirmed or suspected cases of COVID-19 were identified in 272/627 LTC by April 7, 2020. The incidence rate ratio for COVID-19 death was 13.1 (9.9-17.3) relative to community living adults over 69. Incidence rate ratio increased over time and was 87.28 (90% CrI 9.98 to 557.08) by April 7, 2020. Lagged infection in staff was a strong predictor of death in residents (e.g., adjusted IRR for death per infected staff member 1.17, 95% CI 1.11 to 1.26 at a 6-day lag). Interpretation: Mortality risk in elders in Ontario is currently concentrated in LTC, and this risk has increased sharply over a short period of time. Early identification of risk requires a focus on testing and provision of personal protective equipment to staff, and restructuring the LTC workforce to prevent movement of COVID-19 between LTC.

negative: Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.)

negative: Dying in the face of the COVID-19 pandemic: Contextual considerations and clinical recommendations Dying is a natural part of life; however, death is often a fearful, frightening event. Dying in the midst of the COVID-19 pandemic presents challenges that magnify normative fears and may interfere with a healthy grieving process. To maintain a resilient spirit among those who are at risk of losing a loved one or who have lost a family member to COVID-19, it is important that they be provided with the necessary contextually and culturally appropriate skills and resources to facilitate healing in the face of hardship and uncertainty. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

negative: A fast and simple one-step duplex PCR assay for canine distemper virus (CDV) and canine coronavirus (CCoV) detection The one-step polymerase chain reaction (one-step PCR) detection assay is an innovative PCR detection method, eliminating nucleic acid extraction steps, in which samples can be directly added to PCR reagents for testing. For simultaneous detection of CDV and CCoV, a sensitive and specific one-step duplex PCR (one-step dPCR) assay was developed with two pairs of primers that were designed based on H and M gene sequences of CDV and CCoV, respectively. The one-step dPCR with optimized detection conditions has high specificity and sensitivity; independent sequencing assays further verified these results.

negative: Resilience in risk communication networks: Following the 2015 MERS response in South Korea This study investigates regional and local governmental agencies resilience in their use of risk communication with other governmental agencies. Analyses are based on the case of South Korea's response to the 2015 outbreak of the Middle East Respiratory Syndrome Coronavirus. Based on a survey of governmental organizations, the study indicates that governmental agencies seek either reciprocal or redundant communication ties with other governmental agencies while they aim to secure crucial information from high‐level organizations to tackle the transboundary nature of the infectious disease during the outbreak response. Semi‐structured interviews with South Korean officials confirm that subnational governmental agencies rely on the national government and also seek information from other regional and local agencies to improve the resilience in interagency risk communication and to prevent the further transmission of the infectious disease in their local jurisdictions. This study empirically demonstrates how governmental agencies cope with the uncertainty of infectious disease transmission by expanding risk communication channels when hierarchical communication channels and information systems do not meet the needs of outbreak response. The research findings contribute to the understanding of the interactions across organizations in addressing the needs of public health crises that are transboundary in nature and provide important lessons for outbreak responses in South Korea as well as in other countries.

negative: Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries Abstract The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time and the greatest challenge facing the world. Meteorological parameters are reportedly crucial factors affecting respiratory infectious disease epidemics; however, the effect of meteorological parameters on COVID-19 remains controversial. This study investigated the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, which has useful implications for policymakers and the public. Daily data on meteorological conditions, new cases and new deaths of COVID-19 were collected for 166 countries (excluding China) as of March 27, 2020. Log-linear generalized additive model was used to analyze the effects of temperature and relative humidity on daily new cases and daily new deaths of COVID-19, with potential confounders controlled for, including wind speed, median age of the national population, Global Health Security Index, Human Development Index and population density. Our findings revealed that temperature and relative humidity were both negatively related to daily new cases and deaths. A 1 °C increase in temperature was associated with a 3.08% (95% CI: 1.53%, 4.63%) reduction in daily new cases and a 1.19% (95% CI: 0.44%, 1.95%) reduction in daily new deaths, whereas a 1% increase in relative humidity was associated with a 0.85% (95% CI: 0.51%, 1.19%) reduction in daily new cases and a 0.51% (95% CI: 0.34%, 0.67%) reduction in daily new deaths. The results remained robust when different lag structures and the sensitivity analysis were used. These findings provide preliminary evidence that the COVID-19 pandemic may be partially suppressed with temperature and humidity increases. However, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19.

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: History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus. Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a "wet market" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.

negative: Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017 OBJECTIVES: To outline which infectious diseases in the pre-covid-19 era persist in children and adolescents in China and to describe recent trends and variations by age, sex, season, and province. DESIGN: National surveillance studies, 2008-17. SETTING: 31 provinces in mainland China. PARTICIPANTS: 4 959 790 Chinese students aged 6 to 22 years with a diagnosis of any of 44 notifiable infectious diseases. The diseases were categorised into seven groups: quarantinable; vaccine preventable; gastrointestinal and enteroviral; vectorborne; zoonotic; bacterial; and sexually transmitted and bloodborne. MAIN OUTCOME MEASURES: Diagnosis of, and deaths from, 44 notifiable infectious diseases. RESULTS: From 2008 to 2017, 44 notifiable infectious diseases were diagnosed in 4 959 790 participants (3 045 905 males, 1 913 885 females) and there were 2532 deaths (1663 males, 869 females). The leading causes of death among infectious diseases shifted from rabies and tuberculosis to HIV/AIDS, particularly in males. Mortality from infectious diseases decreased steadily from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017. Quarantinable conditions with high mortality have effectively disappeared. The incidence of notifiable infectious diseases in children and adolescents decreased from 280 per 100 000 in 2008 to 162 per 100 000 in 2015, but rose again to 242 per 100 000 in 2017, largely related to mumps and seasonal influenza. Excluding mumps and influenza, the incidence of vaccine preventable diseases fell from 96 per 100 000 in 2008 to 7 per 100 000 in 2017. The incidence of gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline. Vectorborne diseases all declined, with a particularly noticeable reduction in malaria. Zoonotic infections remained at low incidence, but there were still unpredictable outbreaks, such as pandemic A/H1N1 2009 influenza. Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017. Sexually transmitted diseases and bloodborne infections increased significantly, particularly from 2011 to 2017, among which HIV/AIDS increased fivefold, particularly in males. Difference was noticeable between regions, with children and adolescents in western China continuing to carry a disproportionate burden from infectious diseases. CONCLUSIONS: China’s success in infectious disease control in the pre-covid-19 era was notable, with deaths due to infectious diseases in children and adolescents aged 6-22 years becoming rare. Many challenges remain around reducing regional inequalities, scaling-up of vaccination, prevention of further escalation of HIV/AIDS, renewed efforts for persisting diseases, and undertaking early and effective response to highly transmissible seasonal and unpredictable diseases such as that caused by the novel SARS-CoV-2 virus.

negative: A Novel Methodology for Epidemic Risk Assessment: the case of COVID-19 outbreak in Italy We propose a novel data-driven framework for assessing the a-priori epidemic risk of a geographical area and for identifying high-risk areas within a country. Our risk index is evaluated as a function of three different components: the hazard of the disease, the exposure of the area and the vulnerability of its inhabitants. As an application, we discuss the case of COVID-19 outbreak in Italy. We characterize each of the twenty Italian regions by using available historical data on air pollution, human mobility, winter temperature, housing concentration, health care density, population size and age. We find that the epidemic risk is higher in some of the Northern regions with respect to Central and Southern Italy. The corresponding risk index shows correlations with the available official data on the number of infected individuals, patients in intensive care and deceased patients, and can help explaining why regions such as Lombardia, Emilia-Romagna, Piemonte and Veneto have suffered much more than the rest of the country. Although the COVID-19 outbreak started in both North (Lombardia and Veneto) and Central Italy (Lazio) almost at the same time, when the first cases were officially certified at the beginning of 2020, the disease has spread faster and with heavier consequences in regions with higher epidemic risk. Our framework can be extended and tested on other epidemic data, such as those on seasonal flu, and applied to other countries. We also present a policy model connected with our methodology, which helps policy-makers to take informed decisions.

negative: SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy Objective To provide Covid-19 fatality rate, correlations with comorbidities and sensitivity of nasopharingeal swab. Design Prospective cohort study performed between February 21th and March 19rd, 2020 Setting Hospital-based study Participants Of 2,217 admitted, 766 consecutive individuals either reporting or presenting with fever, cough or dyspnea, and suspected to carry Covid-19 infection were examined. Intervention All individuals underwent body temperature and pulse oximetry recording, hematological screening, chest X-ray and/or computed tomography (CT) and SARS-COV-2 assay on nasopharyngeal swab. Onset symptoms, course, comorbidities, number of drugs, use of angiotensin converting enzyme inhibitors and angiotensin-II-receptor antagonists, and follow-up swab, clinical, hematological, and radiological exams, treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Main outcome measures Primary outcomes were non-invasive respiratory support, intensive care unit (ICU) admission, and death. Results Median age of 411 Covid-19 patients was 70.5 years (range 1-99; 66.6% males). CT was positive in 74% and negative in 3.2%. Six patients died within 72 hours; another 66 during hospitalization. Fatality rate was 17.5% (74% males). No death occurred below 60 years. Mortality was 6.6% in 60-69 decade, 21.1% in 70-79, 38.8% in 80-89, and 83.3% above 90 years. Non-invasive respiratory support rate was 27.2%; ICU admission 6.8%. Older age, cough and dyspnea at onset, hypertension, cardiovascular diseases, diabetes, renal insufficiency, >7 drugs intake and positive X-ray at admission were significantly associated with death. Low lymphocyte count, high C-reactive protein, aspartate aminotransferase and lactate dehydrogenase, and low PO2 partial pressure with high lactate at arterial blood gas analysis at admission were also significantly associated with death. Of 32 swab negative patients, 40.6% turned positive at follow-up. Using CT as reference, nasopharyngeal swab had 80% sensitivity. Comorbidity network analysis revealed homogenous distribution of deceased and 60-80 aged patients across diseases. Conclusions Covid-19 caused high mortality among patients older than 70 years and correlated by pre-existing multiorgan impairment irrespective of the age.

negative: Balancing Fiscal and Mortality Impact of SARS-CoV-2 Mitigation Measurements An epidemic carries human and fiscal costs. In the case of imported pandemics, the first-best solution is to restrict national borders to identify and isolate infected individuals. However, when that opportunity is not fully seized and there is no preventative intervention available, second-best options must be chosen. In this article we develop a system of differential equations that simulate both the fiscal and human costs associated to different mitigation measurements. After simulating several scenarios, we conclude that herd immunity (or unleashing the pandemic) is the worst policy in terms of both human and fiscal cost. We found that the second-best policy would be a strict policy (e.g. physical distancing with massive testing) established under the first 20 days after the pandemic, that lowers the probability of infection by 80%. In the case of the US, this strict policy would save more than 239 thousands lives and almost $170.8 billion to taxpayers when compared to the herd immunity case.

negative: Infectious Disease Externalities Abstract In the presence of infectious diseases, people's actions have consequences for others but not ones that they take into account in making their choices. These externalities arise for individuals' decisions about both prevention and therapy and condition the design of government interventions. Subsidies are one form of intervention but may be constrained by circumstances to be less than optimal.

negative: Estimating the burden of SARS-CoV-2 in France France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17th March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 2.6% of infected individuals are hospitalized and 0.53% die, ranging from 0.001% in those <20y to 8.3% in those >80y. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 3.3 to 0.5 (84% reduction). By 11 May, when interventions are scheduled to be eased, we project 3.7 million (range: 2.3-6.7) people, 5.7% of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.

negative: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.

negative: Exploring disaster resilience within the hotel sector: A systematic review of literature Abstract Within the tourism industry, the hotel sector's vulnerabilities are multi-faceted. This literature discussion scrutinizes how disaster and resilience is framed for the tourism sector, and, more specifically, how the concepts can be applied to the hotel sector. A synthesis of the literature points to the importance of prioritizing disaster resilience building for the hotel sector. The body of literature regarding disasters, tourism, and more specifically hotels, has increased over the last 20 years, still improvements in the hotel sector's disaster preparedness and do not appear to be on the same trajectory. Illustrating the predicament of the contemporary hotel industry serves to open a discussion about the value of building resiliency to disaster for hotels. As the numbers of people affected by disasters grows, the importance of providing actionable information to limit the severity of these events on communities also escalates in pace.

negative: Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially 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 difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess 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: Temporal and spatial characteristics of the spread of COVID-19 in Rio de Janeiro state and city From the first cases detected in Wuhan, China, of infections by the disease of the new coronavirus, COVID-19, until the present moment of this pandemic, millions of people have already been infected and hundreds of thousands have died worldwide. The way in which the virus has been dispersed in Brazil, and more specifically in Rio de Janeiro, is the motivation of the present work. Our studies consist of analyzing temporal and spatial characteristics of the spread of COVID-19 in the municipalities of the state of Rio de Janeiro and in the neighborhoods of the state capital, based on open data published by the Health Departments of Governments of the State of RJ and the Municipality of Rio de Janeiro, covering the period from February 27, 2020 to April 27, 2020. For that, we use analysis of time evolution graphs and mappings of spatial distributions and statistics analysis of spatial correlation. Our results suggest that the initial stages of spreading the virus across the state occur exponentially, with specific regions with a higher concentration of rates of cases, deaths and recovered people. In addition, our qualitative and quantitative results, for the data considered, point out that the regions with the highest income average per capita have higher rates of confirmed cases and recovered people, however, the regions of higher lethality do not are found in these places, with several of these regions of high lethality in places of low income per capita. Our results reinforce the idea of creating specific and strategic plans for policies to combat the spread of COVID-19 in the various localities in Rio de Janeiro.

negative: Active surveillance for suspected COVID-19 cases in inpatients with information technology

negative: Immune-epidemiological parameters of the novel coronavirus – a perspective Introduction: At the end of 2019, Wuhan, a city in China with a population of about 11 million, witnessed the outbreak of unusual pneumonia. As of 29 March 2020, the disease has spread to more 199 countries and territories worldwide. The 2019 novel coronavirus, 2019-nCoV, is known as the probable causative agent of the illness. Areas covered: Here, the epidemiological dynamics of the coronavirus disease 2019 (COVID-19) that stand in close relation to distinct immunogenetic characters of the pathogen are discussed, to understand the ability and inability of the immune system in combatting COVID-19. Expert opinion: The elderly population is at increased risk of developing and dying from COVID-19. Comorbidity is present in more than 30% of cases with COVID-19. Except for less than 1% of the total, a chronic condition has been found in all cases that died from COVID-19. Men are more than 1.5 times more likely to die from COVID-19. Evidence links aging to cytokine dysregulation and T-cell repertoire reduction, male population to relatively reduced anti-viral immunity, and COVID-19-related comorbidities to hyper inflammation. The transmission of COVID-19 is influenced by the host-related factors that are known to be associated with immune dysregulation.

negative: Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO. UNLABELLED Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN) antagonists, papain-like protease (PLP) and N protein. Here, we report that the PEDV nsp5 gene, which encodes the 3C-like protease of PEDV, is another IFN antagonist. Mechanistically, the cysteine protease activity of PEDV nsp5 mediates proteolysis of NEMO, the key adaptor for IFN synthesis, and NEMO is cleaved at glutamine 231 (Q231). The new molecular details and determinants impacting NEMO scission by PEDV nsp5 delineated in this study are fundamental to our understanding of critical virus-host interactions that determine PEDV pathogenesis.

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: Jokro: The death of a wild infant chimpanzee from respiratory disease

negative: COVID-19 in Hemodialysis Patients: A Report of 5 Cases In December 2019, an outbreak of coronavirus disease (COVID-19) due to the novel SARS-CoV-2 virus began in China and spread rapidly worldwide. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this Case Report, we describe the clinical and epidemiological features of COVID-19 in 201 maintenance hemodialysis patients in Zhongnan Hospital of Wuhan university, including 5 maintenance hemodialysis patients who contracted COVID-19 disease. Of the 5 patients with COVID-19, one had a definite history of contact with an infected person. The age range of the patients was 47–67 years. Diarrhea (80%), fever (60%), and fatigue (60%) were the most common symptoms. Lymphopenia occurred in all patients.Chest computerized tomography (CT) scans showed ground glass opacity in the lungs of all patients. Up to February 13, 2020, none of the patients had developed severe complications (acute respiratory distress syndrome, shock, multiple organ dysfunction) or died.

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: Science Education in the Light of COVID-19: The Contribution of History, Philosophy and Sociology of Science In this position paper, I examine how the history, philosophy and sociology of science (HPS) can contribute to science education in the era of the COVID-19 pandemic. I discuss shortcomings in the ways that history is often used in school science, and examine how knowledge of previous pandemics might help in teaching about COVID-19. I look at the potential of issues to do with measurement in the context of COVID-19 (e.g. measurement of mortality figures) to introduce school students to issues about philosophy of science, and I show how COVID-19 has the affordance to broaden and deepen the moral philosophy that students typically meet in biology lessons. COVID-19 also provides opportunities to introduce students to sociological ways of thinking, examining data and questioning human practices. It can also enable students to see how science, economics and politics inter-relate. In the final part of the paper, I suggest that there are strong arguments in favour of an interdisciplinary approach in tackling zoonoses like COVID-19 and that there is much to be said for such interdisciplinarity in school science lessons when teaching about socio-scientific issues and issues intended to raise scientific literacy.

negative: Thiopyrano[2,3-d]Thiazoles as New Efficient Scaffolds in Medicinal Chemistry This review presents the up to date development of fused thiopyranothiazoles that comprise one of the thiazolidine derivatives classes. Thiazolidine and thiazolidinone-related compounds belong to the widely studied heterocycles from a medicinal chemistry perspective. From the chemical point of view, they are perfect heterodienes to undergo hetero-Diels–Alder reaction with a variety of dienophiles, yielding regio- and diastereoselectively thiopyranothiazole scaffolds. The annealing of thiazole and thiopyran cycles in condensed heterosystem is a precondition for the “centers conservative” creation of the ligand-target binding complex and can promote a potential selectivity to biotargets. The review covers possible therapeutic applications of thiopyrano[2,3-d]thiazoles, such as anti-inflammatory, antibacterial, anticancer as well as aniparasitic activities. Thus, thiopyrano[2,3-d]thiazoles may be used as powerful tools in the development of biologically active agents and drug-like molecules.

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: Predicting the epidemic trend of COVID-19 in China and across the world using the machine learning approach Background: Although COVID-19 has been well controlled in China, it is rapidly spreading outside the country and may have catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most have used early-stage data and focused on Chinese cases. Methods: We first built models to predict daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on data from January 20, 2020, to March 1, 2020. Based on these models, we built models to predict the epidemic trend across the world (outside China). We also built models to predict the epidemic trend in Italy, Spain, Germany, France, UK, and USA where COVID-19 is rapidly spreading. Findings: The COVID-19 outbreak will have peaked on February 22, 2020, in China and will peak on May 22, 2020, across the world. It will be basically under control in early April 2020 in China and end-August 2020 across the world. The total number of COVID-19 cases will reach around 89,000 in China and 6,126,000 across the world during the epidemic. Around 4,000 and 290,000 people will die of COVID-19 in China and across the world, respectively. The COVID-19 outbreak will have peaked recently in Italy and will peak in Spain, Germany, France, UK, and USA within two weeks. Interpretation: The COVID-19 outbreak is controllable in the foreseeable future if comprehensive and stringent control measures are taken.

negative: Public Health Lessons: Practicing and Teaching Public Health The following four cases represent events that actually occurred at the local, statewide, national, and international levels. A general, succinct overview is provided of each case with references listed should the reader want to access additional resource materials. The concise format of these cases is intended to generate questions. Following the general overview of each case, I examine the lessons learned from the practitioner and educator perspective and I list the skills necessary to address the issues in the case. The reader will note that there are skills that are essential for the public health practitioner to master, whether one is in an internship, entry-level position, or the director of a public health organization and so these skills are consistently listed. I encourage the reader to regularly keep abreast of the news locally and abroad and to set aside time before a staff meeting or supervisory group meeting, or use the first few minutes of a class to discuss these issues. Ask your workforce or students, “Are we ready to handle such an event if it were to occur here?”; “What resources would we need to have accessible?”; “Have we partnered with the correct agencies in the community?”; “Do we have an established, trusted presence in the community?”; “Who else do we need on our team?”; “Do we need training in a specialty area, e.g., emergency preparedness?”; “What skills have we mastered and what skills do we need to obtain?” The discussion-based questions are endless but one runs the risk of not being prepared, either individually, or in their agency, should they not discuss how public health events are occurring around us daily. I encourage you to adapt these selected cases to use in your organization and/or classroom. Discussing these issues and reviewing the lessons learned will only help us to be better prepared public health practitioners and educators of public health students.

negative: Ebola Risk Perception in Germany, 2014 Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.

negative: Acute Respiratory Infections in Persons with Spinal Cord Injury Respiratory disorders are the leading cause of death for persons with both acute and chronic spinal cord injury (SCI), and much of the morbidity and mortality associated with respiratory disorders is related to acute respiratory infections. Pneumonia is the best recognized respiratory infection associated with mortality in this population. Recent evidence supports some management strategies that differ from those recommended for the general population. Upper respiratory tract infections and acute bronchitis may be precipitating factors in the development of pneumonia or ventilatory failure in patients with chronic SCI. This review emphasizes management principles for treatment and prevention of respiratory infections in persons with SCI.

negative: Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

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 3â862â012 individuals (1â957â935 [50·7%] women and 1â904â077 [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 18â374 excess deaths with an RR of 1·5, 36â749 with an RR of 2·0, and 73â498 with an RR of 3·0. In a do nothing scenario, we estimated 146â996 excess deaths with an RR of 1·5, 293â991 with an RR of 2·0, and 587â982 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: Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains. The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.

negative: Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis We performed a meta-analysis to determine safety and efficacy of corticosteroids in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. We searched PubMed, Web of Science, Medline, WanFang Chinese database, and ZhiWang Chinese database using Boolean operators and search terms covering SARS-CoV-2, SARS-CoV, OR MERS-CoV AND corticosteroids to find appropriate studies. Review Manager 5.3 was used to analyze results of meta-analysis. Observational studies were analyzed for quality using the modified Newcastle–Ottawa scale and randomized clinical trials, using the Jadad scale. Subjects were divided into those with severe-only and other (severe and not severe) cohorts based on published criteria. Efficacy endpoints studied included mortality, hospitalization duration, rates of intensive care unit (ICU) admission, use of mechanical ventilation, and a composite endpoint (death, ICU admission, or mechanical ventilation). We included 11 reports including 10 cohort studies and 1 randomized clinical trial involving 5249 subjects (2003–2020). Two discussed the association of corticosteroids and virus clearing and 10 explored how corticosteroids impacted mortality, hospitalization duration, use of mechanical ventilation, and a composite endpoint. Corticosteroid use was associated with delayed virus clearing with a mean difference (MD) = 3.78 days (95% confidence Interval [CI] = 1.16, 6.41 days; I(2) = 0%). There was no significant reduction in deaths with relative Risk Ratio (RR) = 1.07 (90% CI = 0.81; 1.42; I(2) = 80%). Hospitalization duration was prolonged and use of mechanical ventilation increased. In conclusion, corticosteroid use in subjects with SARS-CoV-2, SARS-CoV, and MERS-CoV infections delayed virus clearing and did not convincingly improve survival, reduce hospitalization duration or ICU admission rate and/or use of mechanical ventilation. There were several adverse effects. Because of a preponderance of observational studies in the dataset and selection and publication biases our conclusions, especially regarding SARS-CoV-2, need confirmation in a randomized clinical trial. In the interim we suggest caution using corticosteroids in persons with COVID-19.

negative: Scrutinizing the heterogeneous spreading of COVID-19 outbreak in Brazilian territory After the spread of COVID-19 out of China, the evolution of the pandemic shows remarkable similarities and differences among countries across the world. Eventually, such characteristics are also observed between different regions of the same country. Herewith, we study the heterogeneous spreading of the confirmed infected cases and deaths by the COVID-19 until May 30th, 2020, in the Brazilian territory, which has been seen as the current epicenter of the pandemic in South America. Our first set of results is related to the similarities and it shows that: (i) a power-law growth of the cumulative number of infected people is observed for federative units of the five regions of Brazil; and (ii) the Distance Correlation (DC) calculated between the time series of the most affected federative units and the curve that describes the evolution of the pandemic in Brazil remains about 1 in most of the time, while such quantity calculated for the federative units with a low incidence of newly infected people remains about 0.95. In the second set of results, we focus on the heterogeneous distribution of the confirmed cases and deaths, which is demonstrated by the fact that only three regions concentrate 92% of the cases. By applying the epidemiological SIRD model we estimated the effective reproduction number Re during the pandemic evolution and found that: (i) the mean value of Re for the eight most affected federative units in Brazil is about 2; (ii) the current value of Re for Brazil is greater than 1, which indicates that the epidemic peak is far; and (iii) Ceara was the only federative unit for which the current Re < 1. Based on these findings, we projected the effects of increase or decrease the effective reproduction number and concluded that if the value of Re increases 20%, not only the peak might grow at least 40% but also its occurrence might be anticipated, which hastens the collapse of the public health care system. In all cases, to keep the effective reproduction number 20% below the current one can save thousands of people in the long term.

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: Healthcare impact of COVID-19 epidemic in India: A stochastic mathematical model Abstract Background In India, the SARS-CoV-2 COVID-19 epidemic has grown to 1251 cases and 32 deaths as on 30 Mar 2020. The healthcare impact of the epidemic in India was studied using a stochastic mathematical model. Methods A compartmental SEIR model was developed, in which the flow of individuals through compartments is modeled using a set of differential equations. Different scenarios were modeled with 1000 runs of Monte Carlo simulation each using MATLAB. Hospitalization, intensive care unit (ICU) requirements, and deaths were modeled on SimVoi software. The impact of nonpharmacological interventions (NPIs) including social distancing and lockdown on checking the epidemic was estimated. Results Uninterrupted epidemic in India would have resulted in more than 364 million cases and 1.56 million deaths with peak by mid-July. As per the model, at current growth rate of 1.15, India is likely to reach approximately 3 million cases by 25 May, implying 125,455 (±18,034) hospitalizations, 26,130 (±3298) ICU admissions, and 13,447 (±1819) deaths. This would overwhelm India's healthcare system. The model shows that with immediate institution of NPIs, the epidemic might still be checked by mid-April 2020. It would then result in 241,974 (±33,735) total infections, 10,214 (±1649) hospitalizations, 2121 (±334) ICU admissions, and 1081 (±169) deaths. Conclusion At the current growth rate of epidemic, India's healthcare resources will be overwhelmed by the end of May. With the immediate institution of NPIs, total cases, hospitalizations, ICU requirements, and deaths can be reduced by almost 90%.

negative: Intradural vertebral endarterectomy with nonautologous patch angioplasty for refractory vertebrobasilar ischemia: Case report and literature review. BACKGROUND The natural history of patients with symptomatic vertebrobasilar ischemic symptoms due to chronic bilateral vertebral artery occlusive disease is progressive, and poses significant challenges when refractory to medical therapy. Surgical treatment options depend largely on location and characteristics of the atheroma (s), and generally include percutaneous transluminal angioplasty (PTA) with or without stent placement, posterior circulation revascularization (bypass), extracranial vertebral artery reconstruction, or vertebral artery endarterectomy. CASE DESCRIPTION We present the case of a 56-year-old male with progressive vertebrobasilar ischemia due to tandem lesions in the right vertebral artery at the origin and intracranially in the V4 segment. The contralateral vertebral artery was occluded to the level of posterior inferior cerebellar artery (PICA) and posterior communicating arteries were absent. Following PTA and stent placement at the right vertebral artery origin, the patient was successfully treated with intradural vertebral artery endarterectomy (V4EA) and patch angioplasty via the far lateral approach. Distal endovascular intervention at the V4 segment proved not technically feasible after multiple attempts. CONCLUSIONS V4EA is an uncommonly performed procedure, but may be considered for carefully selected patients. The authors' techniques and indications are discussed. Historical outcomes, relevant anatomic considerations, and lessons learned are reviewed from the literature.

negative: SARS‐coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS Background Angiotensin converting enzyme 2 (ACE2), a monocarboxylase that degrades angiotensin II to angiotensin 1–7, is also the functional receptor for severe acute respiratory syndrome (SARS) coronavirus (SARS‐CoV) and is highly expressed in the lungs and heart. Patients with SARS also suffered from cardiac disease including arrhythmias, sudden cardiac death, and systolic and diastolic dysfunction. Materials and methods We studied mice infected with the human strain of the SARS‐CoV and encephalomyocarditis virus and examined ACE2 mRNA and protein expression. Autopsy heart samples from patients who succumbed to the SARS crisis in Toronto (Canada) were used to investigate the impact of SARS on myocardial structure, inflammation and ACE2 protein expression. Results Pulmonary infection with the human SARS‐CoV in mice led to an ACE2‐dependent myocardial infection with a marked decrease in ACE2 expression confirming a critical role of ACE2 in mediating SARS‐CoV infection in the heart. The SARS‐CoV viral RNA was detected in 35% (7/20) of autopsied human heart samples obtained from patients who succumbed to the SARS crisis during the Toronto SARS outbreak. Macrophage‐specific staining showed a marked increase in macrophage infiltration with evidence of myocardial damage in patients who had SARS‐CoV in their hearts. The presence of SARS‐CoV in the heart was also associated with marked reductions in ACE2 protein expression. Conclusions Our data show that SARS‐CoV can mediate myocardial inflammation and damage associated with down‐regulation of myocardial ACE2 system, which may be responsible for the myocardial dysfunction and adverse cardiac outcomes in patients with SARS.

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: The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged infection in humans affecting the Arabian Peninsula, Europe, and North Africa. The source and persistence of the infection in humans remains unknown. The aim of this paper was to apply a risk analysis approach to the epidemiology of MERS-CoV and to understand the source of ongoing infections. The epidemiology of MERS-CoV was reviewed and compared to SARS. Each observed feature of MERS-CoV epidemiology was summarized and fitted to either an epidemic or one of two sporadic scenarios (either animal or deliberate release). As of May 2014, MERS-CoV has infected over 681 people and killed a further 204 over 2 years. In contrast, there were 8,273 cases and 775 deaths from SARS within 8 months. MERS-CoV has a more sporadic pattern unlike the clear epidemic pattern seen with SARS, and an unusual concentration of cases in the Middle East, without epidemics in other countries to which it has spread. SARS, with a higher reproductive number (R0), was eliminated from humans within 8 months of emerging, yet MERS-CoV, with a low R0 has persisted in humans over a far more prolonged period. This is at odds with the expected behavior of a virus with a low R0, which theoretically should not persist unless there are ongoing introductions of infection into humans, and poses the question “what is the source of continuing infections in humans?” A hospital outbreak in Al Ahsa, the Kingdom of Saudi Arabia (KSA), had a classic epidemic pattern with some human-to-human transmission. However, 3 different strains were identified in that outbreak, an unexpected and unexplained finding for what appears to be a single source outbreak. Since this outbreak in April 2013, there has been a large increase in new cases, mainly in KSA in April and May 2014, with no corresponding epidemics in other countries. Yet MERS-CoV was present in KSA over several mass gatherings (which predispose to epidemics), including the Hajj pilgrimage, without an epidemic arising. Furthermore, although the virus has been identified in bats and camels, the mode of ongoing transmission to humans remains uncertain. Although some cases appear to be transmitted from human to human, and a few have animal or camel exposure, many cases have no history of contact with either animals or human cases. A high proportion of asymptomatic or otherwise undetected cases have been postulated as an explanation for the unusual epidemiology, yet active surveillance does not support this. When the observed data were fitted to different disease patterns, the features of MERS-CoV fit better with a sporadic pattern, with evidence for either deliberate release or an animal source. There are many discrepancies in the observed epidemiology of MERS-CoV, which better fits a sporadic than an epidemic pattern. Possible explanations of the unusual features of the epidemiology include human-to-human transmission with a large proportion of undetected cases; or sporadic ongoing infections from a non-human source; or a combination of both. Possible sources of ongoing sporadic infection in humans include animals (camels appear the most likely source), or deliberate release. The latter could explain 3 strains being present in a single hospital outbreak. Genetic testing should be conducted to determine whether the virus is evolving to be more transmissible. Better ascertainment of mild or asymptomatic cases is also needed. Finally, the discrepant epidemiology warrants critical analysis of all possible explanations, and involvement of all stakeholders in biosecurity, and deliberate release must be seriously considered and at least acknowledged as a possibility.

negative: Communication, collaboration and cooperation can stop the 2019 coronavirus As the outbreak of a deadly new coronavirus in China and its rapid spread is rattling countries, only the collective international experience and advances derived from past outbreaks can accelerate its control.

negative: Emerging Viruses Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs.

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: Tracking the reach of COVID-19 kin loss with a bereavement multiplier applied to the United States The coronavirus disease 2019 (COVID-19) pandemic has led to a large increase in mortality in the United States and around the world, leaving many grieving the sudden loss of family members. We created an indicator-the COVID-19 bereavement multiplier-that estimates the average number of individuals who will experience the death of a close relative (defined as a grandparent, parent, sibling, spouse, or child) for each COVID-19 death. Using demographic microsimulation-based estimates of kinship networks in the United States, the clear age gradient in COVID-19 mortality seen across contexts, and several hypothetical infection prevalence scenarios, we estimate COVID-19 bereavement multipliers for White and Black individuals in the United States. Our analysis shows that for every COVID-19 death, approximately nine surviving Americans will lose a grandparent, parent, sibling, spouse, or child. These estimates imply, for example, that if 190,000 Americans die from COVID-19, as some models project, then â¼1.7 million will experience the death of a close relative. We demonstrate that our estimates of the bereavement multiplier are stable across epidemiological realities, including infection scenarios, total number of deaths, and the distribution of deaths, which means researchers can estimate the bereavement burden over the course of the epidemic in lockstep with rising death tolls. In addition, we provide estimates of bereavement multipliers by age group, types of kin loss, and race to illuminate prospective disparities. The bereavement multiplier is a useful indicator for tracking COVID-19's multiplicative impact as it reverberates across American families and can be tailored to other causes of death.

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: Upheaval in cancer care during the COVID-19 outbreak On Monday, 23 March 2020, Nigeria recorded its first mortality from the novel global COVID-19 outbreak. Before this, the country reported 36 confirmed cases (at the time of writing) and has discharged home two cases after weeks of care at a government-approved isolation centre in Lagos State. This first mortality was that of a 67-year-old man with a history of multiple myeloma, a type of blood cancer. He was undergoing chemotherapy and had just returned to Nigeria following medical treatment in the United Kingdom. The novel COVID-19 pandemic has grounded several global activities including the provision of health care services to people with chronic conditions such as cancer. Evidence from China suggests that cancer patients with COVID-19 infection are a vulnerable group, with a higher risk of severe illness resulting in intensive care unit admissions or death, particularly if they received chemotherapy or surgery. This letter is an attempt to suggest practicable interventions such as the use of existing digital health platforms to limit patients’ and oncology professionals’ physical interactions as a way of reducing the risk of COVID-19 infection transmission amongst cancer patients and oncologists, as well as outlining effective strategies to ensure that cancer care is not completely disrupted during the outbreak.

negative: Pseudo acute myocardial infarction in a young COVID-19 patient Abstract: A 29 year old man tested positive for COVID-19 and developed acute respiratory distress syndrome (ARDS). While mechanically ventilated, his electrocardiogram (EKG) showed inferior ST segment elevations, with normal serial cardiac troponin I and transthoracic echocardiograms. He was treated conservatively, with complete clinical recovery and resolution of his EKG abnormalities.

negative: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3(–/–)), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3(–/–) mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3(–/–) mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3(–/–) mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.

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: COVID-19 on cruise ships: preventive quarantine or abandonment of patients?

negative: A Method to Identify the Missing COVID-19 Cases in the U.S. and Results for mid-April 2020 I use the COVID-19 death rate in South Korea and a method relating the ratio of death rates in a U.S. state to its share of cumulative positive tests to estimate the total cases of COVID-19 in the U.S. and to estimate the extent of infection and the unidentified share of the infected population in each of the lower-48 states and in New York City in mid-April, 2020. I identify a logarithmic relationship between the cumulative death rate in a state and its cumulative positive share of tests. Using this relationship, I find that 4.3-5.4 million people, 1.4-1.7% of the U.S. population, were infected, with rates of infection that ranged from 0.1% in more rural states to 8-10% in New York state and 11-13% in New York City. Only 16-20% of these infected individuals were identified later through testing.

negative: The ethical challenges of the SARS‐CoV‐2 pandemic in the global south and the global north – same and different The global COVID‐19 death toll stands at the time of writing at 163,500. By the time you read this, that number will have increased significantly, and it is likely that we won’t have seen the end of it by that time. Policy makers in both the global north as well as the global south rose to the challenge, with decidedly mixed responses as well as decidedly mixed results, as comparisons between reported case loads of, say the UK and Germany or between Brazil and the PR of China, show. Discipline specific responses translated into many global collaborative efforts aimed at developing treatments, modelling of the impact of varying policy options on the continuing pandemic, preventive vaccine trials, and so on and so forth.

negative: Using rapid online surveys to assess perceptions during infectious disease outbreaks: a cross-sectional survey on Covid-19 among the general public in the United States and United Kingdom Background: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate in phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. Objective: To apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (Covid-19) among the general public in the United States (US) and the United Kingdom (UK). Methods: An online questionnaire was administered to 3,000 adults residing in the US and 3,000 adults residing in the UK who had registered with Prolific Academic to participate in online research. Strata by age (18 - 27, 28 - 37, 38 - 47, 48 - 57, or >=58 years), sex (male or female), and ethnicity (White, Black or African American, Asian or Asian Indian, Mixed, or "Other"), and all permutations of these strata, were established. The number of participants who could enrol in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrolment into the survey within the strata was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2 2020. Results: 2,986 and 2,988 adults residing in the US and the UK, respectively, completed the questionnaire. 64.4% (1,924/2,986) of US and 51.5% (1,540/2,988) of UK participants had a tertiary education degree. 67.5% (2,015/2,986) of US participants had a total household income between $20,000 and $99,999, and 74.4% (2,223/2,988) of UK participants had a total household income between GBP15,000 and GBP74,999. US and UK participants' median estimate for the probability of a fatal disease course among those infected with SARS-CoV-2 was 5.0% (IQR: 2.0% - 15.0%) and 3.0% (IQR: 2.0% - 10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of Covid-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI: 36.1% - 39.6%) of US and 29.7% (95% CI: 28.1% - 31.4%) of UK participants thought that wearing a common surgical mask was 'highly effective' in protecting them from acquiring Covid-19. 25.6% (95% CI: 24.1% - 27.2%) of US and 29.6% (95% CI: 28.0% - 31.3%) of UK participants thought it prudent to refrain from eating at Chinese restaurants. Around half (53.8% [95% CI: 52.1% - 55.6%] of US and 39.1% [95% CI: 37.4% - 40.9%] of UK participants) thought that children were at an especially high risk of death when infected with SARS-CoV-2. Conclusions: The distribution of participants by total household income and education followed approximately that of the general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public's knowledge and misperceptions during rapidly moving infectious disease outbreaks.

negative: Mortality Analysis of COVID-19 Confirmed cases in Pakistan Introduction: COVID-19, a novel disease, appeared in December 2019 in China and rapidly spread across the world. Till the second week of April 2020, high incidence (2.9/100,000) and cases fatality rates (1.7%) were observed in Pakistan. This study was conducted to determine the temporal and spatial distribution of the first 100 deaths attributed to COVID-19 in Pakistan and their associated demographic factors. Method: We conducted a descriptive epidemiological analysis of the first 100 deaths reported among RT-PCR confirmed COVID-19 cases. Demographic, epidemiological, and risk factors information was obtained associated comorbidities and clinical signs and symptoms were recorded and frequencies were determined. Results: A total of 100 mortalities with overall Case Fatality Rate 1.67% (CFR) were analysed. Median age of patients was 64.5 years (IQR: 54-70) with 75% (n=75) Males. Among all deaths reported, 71 (71%) cases had one or more documented comorbidities at the time of diagnosis. Most frequently reported co-morbidities were; hypertension (67 %), followed by Diabetes Mellitus 945%) and Ischemic Heart Diseases (27%). First death was reported on 18 March 2020 and the most frequent presenting symptoms were shortness of breath (87%) and fever (79%). Median duration of illness was eight days (IQR: 4-11 days), the median delay reaching hospital to seek health care was three days (IQR: 0-6 days) while median duration of hospital stay was also three days (IQR: 1-7 days). Among all reported deaths, 62% were attributed to local transmission as these cases had no history of international travel. The most affected age group was 60-69 years while no death reported in age group below 20 years. Conclusion: High CFR among old age group and its association with co-morbidities (chronic disease) suggests targeted interventions such as social distancing and strict quarantine measure for elderly and morbid people. Comparative studies among deaths and recovered patients are recommended to explore further disease dynamics. Key words: COVID-19, Cases Fatality Rates, Co-morbidities, Epidemiology, Pakistan, Co-morbidities

negative: A mathematical model for estimating the age-specific transmissibility of a novel coronavirus Background: A novel coronavirus named as "SARS-CoV-2" has spread widely in many countries since December 2019, especially in China. This study aimed to quantify the age-specific transmissibility by using a mathematical model. Methods: An age-specific susceptible - exposed - symptomatic - asymptomatic - recovered - seafood market (SEIARW) model was developed based on two suspected transmission routes (from market to person and person to person). The susceptible people from Wuhan City were divided into different age groups. We used the subscript i and j to represent age group 1 to 4 (1: <= 14 years; 2: 15-44 years; 3: 45-64 years; 4: >= 65 years) and 1 to 5 (1: <= 5 years; 2: 6-14 years; 3: 15-24 years; 4: 25-59 years; 4: >= 60 years), respectively. Data of reported COVID-19 cases were collected from one published literature from 26 November to 22 December, 2019 in Wuhan City, China. The age-specific transmissibility of the virus was estimated accordingly secondary attack rate (SAR). Results: The age-specific SEIARW model fitted with the reported data well by dividing the population into four age groups (χ2 = 4.99 × 10-6, P > 0.999), and five age groups (χ2 = 4.85 × 10-6, P > 0.999). Based on the four-age-group SEIARW model, the highest transmissibility occurred from age group 2 to 3 (SAR23 = 17.56 per 10 million persons), followed by from age group 3 to 2 (SAR32 = 10.17 per 10 million persons). The lowest transmissibility occurred from age group 1 to 2 (SAR12 = 0.002 per 10 million persons). Based on the five-age-group SEIARW model, the highest transmissibility occurred from age group 4 to 5 (SAR45 = 12.40 per 10 million persons), followed by from age group 5 to 4 (SAR54 = 6.61 per 10 million persons). The lowest transmissibility occurred from age group 3 to 4 (SAR34 = 0.0002 per 10 million persons). Conclusions: SARS-CoV-2 has high transmissibility among adults and elder people but low transmissibility among children and young people.

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: International Committee of the Red Cross (ICRC): General guidance for the management of the dead related to COVID-19 Abstract Based on its forensic capacity and experience gained worldwide from the management of the dead in emergencies, including epidemics, the International Committee of the Red Cross has been asked by the authorities and other relevant stakeholders in some of its operational contexts to advise on the management of the dead from COVID-19 infection, for which it has prepared the following guidance. This includes advice on the handling of COVID-19 fatalities and a set of considerations for managers faced with the need to plan for adequately responding to a possible surge in fatalities caused by COVID-19.

negative: Coronavirus (COVID-19) Outbreak: What the Department of Radiology Should Know Abstract In December 2019, a novel coronavirus (COVID-19) pneumonia emerged in Wuhan, China. Since then, this highly contagious COVID-19 has been spreading worldwide, with a rapid rise in the number of deaths. Novel COVID-19–infected pneumonia (NCIP) is characterized by fever, fatigue, dry cough, and dyspnea. A variety of chest imaging features have been reported, similar to those found in other types of coronavirus syndromes. The purpose of the present review is to briefly discuss the known epidemiology and the imaging findings of coronavirus syndromes, with a focus on the reported imaging findings of NCIP. Moreover, the authors review precautions and safety measures for radiology department personnel to manage patients with known or suspected NCIP. Implementation of a robust plan in the radiology department is required to prevent further transmission of the virus to patients and department staff members.

negative: After Less Than 2 Months, the Simulations That Drove the World to Strict Lockdown Appear to be Wrong, the Same of the Policies They Generated Here, we review modeling predictions for Covid-19 mortality based on recent data. The Imperial College model trusted by the British Government predicted peak mortalities above 170 deaths per million in the United States, and above 215 deaths per million in Great Britain, after more than 2 months from the outbreak, and a length for the outbreak well above 4 months. These predictions drove the world to adopt harsh distancing measures and forget the concept of herd immunity. China had peak mortalities of less than 0.1 deaths per million after 40 days since first deaths, and an 80-day-long outbreak. Italy, Belgium, the Netherlands, Sweden, or Great Britain flattened the curve at 13.6, 28.6, 9.0, 10.6, and 13.9 deaths per million after 40, 39, 33, 44, and 39 days from first deaths, or 31, 29, 24, 38, and 29 days since the daily confirmed deaths reached 0.1 per million people, respectively. The declining curve is much slower for Italy, the Netherlands, or Great Britain than Belgium or Sweden. Opposite to Great Britain, Italy, or Belgium that enforced a complete lockdown, the Netherlands only adopted an “intelligent” lockdown, and Sweden did not adopt any lockdown. However, they achieved better results. Coupled to new evidence for minimal impact of Covid-19 on the healthy population, with the most part not infected even if challenged, or only mild or asymptomatic if infected, there are many good reasons to question the validity of the specific epidemiological model simulations and the policies they produced. Fewer restrictions on the healthy while better protecting the vulnerable would have been a much better option, permitting more sustainable protection of countries otherwise at risk of second waves as soon as the strict measures are lifted.

negative: Modelling the Potential Health Impact of the COVID-19 Pandemic on a Hypothetical European Country A SEIR simulation model for the COVID-19 pandemic was developed (http://covidsim.eu) and applied to a hypothetical European country of 10 million population. Our results show which interventions potentially push the epidemic peak into the subsequent year (when vaccinations may be available) or which fail. Different levels of control (via contact reduction) resulted in 22% to 63% of the population sick, 0.2% to 0.6% hospitalised, and 0.07% to 0.28% dead (n=6,450 to 28,228).

negative: Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006)

negative: Epidemic Situation of Novel Coronavirus Pneumonia in China mainland [Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to February 14, 2020, Analysis of 66,492 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to February 14, 2020, a total of 66,492 cases of NCP were confirmed in China mainland, a total of 54,406 cases were confirmed in Hubei Province, a total of 37,914 cases were confirmed in Wuhan city. On February 5, 2020, the number of suspected cases of NCP in China mainland reached a maximum of 5,328. Since then, the suspected cases have shown a significant downward trend. On February 4, 2020, the number of confirmed cases has gradually decreased in China mainland since then. On February 12, 2020, the number of confirmed cases of NCP in China mainland increased explosively to 15,152, and then began to decline. From February 3, 2020, except for Hubei Province, In China mainland, the number of newly confirmed cases of NCP has continued to decline; From December 1, 2019 to February 14, 2020, a total of 1,523 cases of NCP deaths in China mainland, a cumulative cure of 8096 cases, and mortality and cure rate were 2.29% (1523/66492) and 12.18% (8096/66492) respectively; Starting from January 27, 2020, The spread index of NCP gradually declined, and the extinction index of NCP rose little by little from January 29, 2020. [Conclusion] Starting from February 5, 2020, the number of suspected cases of the NCP is gradually decrease in China mainland. From February 3, 2020, the number of newly confirmed cases of NCP is continuous decline in China mainland except Hubei Province, This shows that the control of the transmission of NCP has achieved. Judged from the number of confirmed cases of NCP, controlling the outbreak in China mainland is to control the epidemic in Hubei province, and the key to controlling the outbreak in Hubei province is to control the epidemic in Wuhan city; Judging from the gradual increase in the number and cure rate of the NCP, and the gradual decline in the number of deaths and mortality, the trend of outbreak control and treatment is getting better; A decrease of the NCP spread index indicates a slowdown in the spread of the virus, but the cumulative confirmed cases is still increase, so the epidemic will continue for some time. However, the turning point of the epidemic in mainland China has not yet occurred. On February 12, 2020, the turning point of the epidemic in China mainland except Hubei province, has turned up.

negative: Modified Bhramari Pranayama in Covid 19 Infection The Coronavirus (2019-Cov-2) infection Covid-19 is highly contagious caused by single stranded RNA virus (+ssRNA) with nucleocapsid and spreading widely all across the world and responsible for more than 3.6 million morbidity and 0.25 million mortality No specific treatment is available till date. The clinical symptoms are mainly upper respiratory leading to diffuse viral pneumonia and multiple organ failure involving. Kidney, Liver and Heart along with coagulopathies. During 2004 (SARS-CoV) pandemic role of nitric oxide in its management is well demonstrated. Nitric Oxide (NO) reversed pulmonary hypertension. Improved severe hypoxia and shortened the stay in ICU and ventilatory support. Nitric Oxide increased the survival rate. The genetic composition of Corona Virus (SARS-CoV) is almost similar to Covid-19, thus indicates good chances of effectiveness or enhancement in results by Nitric Oxide along with other modes in treatment of Covid-19. It has been proved by studies by serendipity humming increases NO Expression dramatically.It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold. Hypoxia in ARD Syndrome leads to blood coagulation by depression of body defence anticoagulatory and fibrolytic properties along with metabolic acidosis. If we go into hypoxic hypercapnic state no hyper coagulation takes place. Hence Bhramari by enhancing the expression of Nitric Oxide and increased Carbon dioxide by extended exhalation and alkaline pH prevents coagulopathies and morbidity due to Covid-19.

negative: Modeling the COVID-19 outbreak in the United States The COVID-19 contagion has developed at an alarming rate in the US and as of April 24, 2020, tens of thousands of people have already died from the disease. In the event of an outbreak like such, forecasting the extent of the mortality that will occur is crucial to aid the implementation of effective interventions. Mortality depends on two factors: the case fatality rate and the case incidence. We combine a cohort-based model that determines case fatality rates along with a modified logistic model that evaluates the case incidence to determine the number of deaths in all the US states over time; the model is also able to include the impact of interventions. Both models yield exceptional goodness-of-fit. The model predicted a range of death outcomes (79k to 246k) all of which are considerably greater than the figures presented in mainstream media. This model can be used more effectively than current models to estimate the number of deaths during an outbreak, allowing for better planning.

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: Emerging and reemerging respiratory viral infections up to Covid-19 Infectious diseases remain as the significant causes of human and animal morbidity and mortality, leading to extensive outbreaks and epidemics. Acute respiratory viral diseases claim over 4 million deaths and cause millions of hospitalizations in developing countries every year. Emerging viruses, especially the RNA viruses, are more pathogenic since most people have no herd immunity. The RNA viruses can adapt to the rapidly changing global and local environment due to the high error rate of their polymerases that replicate their genomes. Currently, coronavirus disease 2019 (COVID-19) is determined as an u28a9 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in 2019 in u28ac. Herein we discuss emerging and reemerging respiratory viral infections till to SARS-CoV-2.

negative: Impact of COVID-19 on maxillofacial surgery practice: a worldwide survey Abstract The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changing our habits. To date, April 12, 2020, the virus has reached 209 nations, affecting 1.8 million people and causing more than 110,000 deaths. Maxillofacial surgery represents an example of a specialty that has had to adapt to this outbreak, because of the subspecialties of oncology and traumatology. The aim of this study was to examine the effect of this outbreak on the specialty of maxillofacial surgery and how the current situation is being managed on a worldwide scale. To achieve this goal, the authors developed an anonymous questionnaire which was posted on the internet and also sent to maxillofacial surgeons around the globe using membership lists from various subspecialty associations. The questionnaire asked for information about the COVID-19 situation in the respondent’s country and in their workplace, and what changes they were facing in their practices in light of the outbreak. The objective was not only to collect and analyse data, but also to highlight what the specialty is facing and how it is handling the situation, in the hope that this information will be useful as a reference in the future, not only for this specialty, but also for others, should COVID-19 or a similar global threat arise again.

negative: Forecasting of COVID-19 Cases and Deaths Using ARIMA Models After the outbreak of severe acute respiratory syndrome (SARS-2002/2003) and middle east respiratory syndrome (MERS-2012/2014) in the world, new public health crisis, called new coronavirus disease (COVID-19), started in China in December 2019 and has spread all over countries. COVID-19 coronavirus has been global threat of the disease and infected humans rapidly. Control of the pandemi is urgently essential, and science community have continued to research treatment agents. Support therapy and intensive care units in hospitals are also efective to overcome of COVID-19. Statistic forecasting models could aid to healthcare system in preventation of COVID-19. This study aimed to compose of forecasting model that could be practical to predict the spread of COVID-19 in Italy, Spain and Turkey. For this purpose, we performed Auto Regressive Integrated Moving Average (ARIMA) model on the European Centre for Disease Prevention and Control COVID-19 data to predict the number of cases and deaths in COVID-19. According to the our results, while number of cases in Italy and Spain is expected to decrease as of July, in Turkey is expected to decline as of September. The number of deaths in Italy and Spain is expected to be the lowest in July. In Turkey, this number is expected to reach the highest in July. In addition, it is thought that if studies in which the sensitivity and validity of this method are tested with more cases, they will contribute to researchers working in this field. KEYWORDS: COVID-19, pandemi, ARIMA, time series analysis

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: Registries Offer Insights on COVID-19-Cancer Connection Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.

negative: COVID-19 und die Niere The drastic consequences that emerging infectious diseases can have for people and society are currently being demonstrated by coronavirus disease 2019 (COVID-19). Since its initial description in December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dominated current scientific and public interest.

negative: Forecasting COVID-19 impact on hospital bed-days, ICU-days, ventilator-days and deaths by US state in the next 4 months Key Points Question: Assuming social distancing measures are maintained, what are the forecasted gaps in available health service resources and number of deaths from the COVID-19 pandemic for each state in the United States? Findings: Using a statistical model, we predict excess demand will be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds at the peak of COVID-19. Peak ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674) ventilators. Peak demand will be in the second week of April. We estimate 81,114 (95% UI 38,242 to 162,106) deaths in the United States from COVID-19 over the next 4 months. Meaning: Even with social distancing measures enacted and sustained, the peak demand for hospital services due to the COVID-19 pandemic is likely going to exceed capacity substantially. Alongside the implementation and enforcement of social distancing measures, there is an urgent need to develop and implement plans to reduce non-COVID-19 demand for and temporarily increase capacity of health facilities. Abstract Importance: This study presents the first set of estimates of predicted health service utilization and deaths due to COVID-19 by day for the next 4 months for each state in the US. Objective: To determine the extent and timing of deaths and excess demand for hospital services due to COVID-19 in the US. Design, Setting, and Participants: This study used data on confirmed COVID-19 deaths by day from WHO websites and local and national governments; data on hospital capacity and utilization for US states; and observed COVID-19 utilization data from select locations to develop a statistical model forecasting deaths and hospital utilization against capacity by state for the US over the next 4 months. Exposure(s): COVID-19. Main outcome(s) and measure(s): Deaths, bed and ICU occupancy, and ventilator use. Results: Compared to licensed capacity and average annual occupancy rates, excess demand from COVID-19 at the peak of the pandemic in the second week of April is predicted to be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds. At the peak of the pandemic, ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674). The date of peak excess demand by state varies from the second week of April through May. We estimate that there will a total of 81,114 (95% UI 38,242 to 162,106) deaths from COVID-19 over the next 4 months in the US. Deaths from COVID-19 are estimated to drop below 10 deaths per day between May 31 and June 6. Conclusions and Relevance: In addition to a large number of deaths from COVID-19, the epidemic in the US will place a load well beyond the current capacity of hospitals to manage, especially for ICU care. These estimates can help inform the development and implementation of strategies to mitigate this gap, including reducing non-COVID-19 demand for services and temporarily increasing system capacity. These are urgently needed given that peak volumes are estimated to be only three weeks away. The estimated excess demand on hospital systems is predicated on the enactment of social distancing measures in all states that have not done so already within the next week and maintenance of these measures throughout the epidemic, emphasizing the importance of implementing, enforcing, and maintaining these measures to mitigate hospital system overload and prevent deaths.

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: 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: The role of environmental factors to transmission of SARS-CoV-2 (COVID-19) The current outbreak of the novel coronavirus disease 2019 (COVID-19) in more than 250 countries has become a serious threat to the health of people around the world. Human-to-human transmission of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs most often when people are in the incubation stage of the disease or are carriers and have no symptoms. Therefore, in this study, was discussed the role of environmental factors and conditions such as temperature, humidity, wind speed as well as food, water and sewage, air, insects, inanimate surfaces, and hands in COVID-19 transmission. The results of studies on the stability of the SARS-CoV-2 on different levels showed that the resistance of this virus on smooth surfaces was higher than others. Temperature increase and sunlight can facilitate the destruction of SARS-COV-2 and the stability of it on surfaces. When the minimum ambient air temperature increases by 1 °C, the cumulative number of cases decreases by 0.86%. According to the latest evidence, the presence of coronavirus in the sewer has been confirmed, but there is no evidence that it is transmitted through sewage or contaminated drinking water. Also, SARS-COV-2 transmission through food, food packages, and food handlers has not been identified as a risk factor for the disease. According to the latest studies, the possibility of transmitting SARS-COV-2 bioaerosol through the air has been reported in the internal environment of ophthalmology. The results additionally show that infectious bio-aerosols can move up to 6 feet. There have been no reports of SARS-COV-2 transmission by blood-feeding arthropods such as mosquitoes.

negative: The effect of uncontrolled travelers and social distancing on the spread of novel coronavirus disease (COVID-19) in Colombia

negative: Deep Learning and Holt-Trend Algorithms for predicting COVID-19 pandemic According to WHO, more than one million individuals are infected with COVID-19, and around 20000 people have died because of this infectious disease around the world. In addition, COVID-19 epidemic poses serious public health threat to the world where people with little or no pre-existing human immunity can be more vulnerable to the effects of the effects of the coronavirus. Thus, developing surveillance systems for predicting COVID-19 pandemic in an early stage saves millions of lives. In this study, the deep learning algorithm and Holt-trend model is proposed to predict coronavirus. The Long-Short Term Memory (LSTM ) algorithm and Holt-trend were applied to predict confirmed numbers and death cases. The real time data have been collected from the World Health Organization (WHO) . In the proposed research, we have considered three countries to test the proposed model namely Saudi Arabia, Spain and Italy. The results suggest that the LSTM models showed better performance in predicting the cases of coronavirus patients. Standard measure performance MSE, RMSE, Mean error and correlation are employed to estimate the results of the proposed models. The empirical results of the LSTM by using correlation metric are 99.94%, 99.94% and 99.91 to predict number of confirmed cases on COVID-19 in three countries. Regarding the prediction results of LSTM model to predict the number of death on COVID-19 are 99.86%, 98.876% and 99.16 with respect to the Saudi Arabia, Italy and Spain respectively. Similarly the experimented results of Holt-Trend to predict the number of confirmed cases on COVID-19 by using correlation metrics are 99.06%, 99.96% and 99.94, whereas the results of Holt-Trend to predict the number of death cases are 99.80%, 99.96 and 99.94 with respect to the Saudi Arabia, Italy and Spain respectively. The empirical results indicate the efficient performance of the presented model in predicting the number of confirmed and death cases of COVID-19 in these countries. Such findings provide better insights about the future of COVID-19 in general. The results were obtained by applying the time series models which needs to be considered for the sake of saving the lives of many people.

negative: Pathological Clues to How the SARS Virus Kills

negative: Hospitalization time and outcome in patients with Coronavirus Disease 2019 (COVID-19): analysis data from China Objective: The mean hospitalization time and outcome among patients with coronavirus disease 2019 (COVID-19) was estimated with the purpose of providing evidence for decision-making in medical institutions and governments in epidemic areas. Method：The data of COVID-19 patients in china were collected from the websites of provincial and municipal health commissions. The mean hospitalization time and mortality in the mild or severe patients and the mean time from severe to mild illness were calculated by Gaussian mixture modeling. Results: The mean hospitalization time among mild patients in Hubei province, other areas except Hubei province, and the national areas was 20.71 ± 9.30, 16.86 ± 8.24, and 19.34 ± 9.29 days, respectively. The mean transition time from severe to mild illness in the above three areas were 15.00, 17.00, and 14.99 days, respectively. The death rate of mild and severe patients in Hubei province and the national areas were 1.10% and 18.14%, and 1.10% and 17.70%, respectively. Among those patients who died of COVID-19, the mean time from severe transition to death in Hubei province and the national areas was 6.22 ± 5.12 and 6.35 ± 5.27 days, respectively. Conclusion: There were regional differences in the average length of stay between Hubei province and other regions, which may be related to different medical configurations. For those severe patients who died of COVID-19, the average time from hospitalization to death was about one week, and proper and effective treatments in the first week were critical.

negative: Assessing the risks of "infodemics" in response to COVID-19 epidemics Our society is built on a complex web of interdependencies whose effects become manifest during extraordinary events such as the COVID-19 pandemic, with shocks in one system propagating to the others to an exceptional extent. We analyzed more than 100 millions Twitter messages posted worldwide in 64 languages during the epidemic emergency due to SARS-CoV-2 and classified the reliability of news diffused. We found that waves of unreliable and low-quality information anticipate the epidemic ones, exposing entire countries to irrational social behavior and serious threats for public health. When the epidemics hit the same area, reliable information is quickly inoculated, like antibodies, and the system shifts focus towards certified informational sources. Contrary to mainstream beliefs, we show that human response to falsehood exhibits early-warning signals that might be mitigated with adequate communication strategies.

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: Die Bedeutung von Coronaviren: Das Beispiel SARS The emergence of the new SARS coronavirus has shown dramatically the high relevance of human coronavirus infections. This overview presents data of both epidemiological and clinical studies of this new virus infection. Moreover, details of research on the pathogenesis, diagnostics, and therapy are given. The recent infections in December 2003 clearly document that SARS will be a major topic also in 2004.

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: COVID-19 Myocarditis and Severity Factors： An Adult Cohort Study Background Notwithstanding the clinical hallmarks of COVID-19 patients were reported, several critical issues still remain mysterious, i.e., prognostic factors for COVID-19 including extrinsic factors as viral load of SARS-CoV-2 and intrinsic factors as individual's health conditions; myocarditis incidence rate and hallmarks. Methods Demographic, epidemiologic, radiologic and laboratory data were collected by medical record reviews of adult hospitalized patients diagnosed as COVID-19. Cycle threshold (Ct) value data of real-time PCR (RT-PCR) were collected. The time duration was from 21 January to 2 March, 2020. Pulmonary inflammation index (PII) values were used for chest CT findings. Multivariate logistic regression analysis was used to identify independent severity risk factors. RESULTS In total, 84 hospitalized adult patients diagnosed as COVID-19 were included, including 20 severe and 64 nonsevere cases. The viral load of the severe group was significantly higher than that of the non-severe group, regardless of the Ct values for N or ORF1ab gene of virus (all p<0.05).Typical CT abnormalities was more likely existing in the severe group than in the nonsevere group in patchy shadows or ground glass opacities, consolidation, and interlobular septal thickening (all p<0.05). In addition, the PII values in the severe group was significantly higher than that in the nonsevere group (52.5 [42.5-62.5] vs 20 [5.0-31.6]; p<0.001). Amongst 84 patients, 13 patients (15.48%) were noted with abnormal electrocardiograms (ECGs) and serum myocardial enzyme levels; whereas 4 (4.8%) were clinically diagnosed as SARS-CoV-2 myocarditis. Multivariable logistic regress analysis distinguished three key independent risk factors for the severity of COVID-19, including age [OR 2.350; 95% CI (1.206 to 4.580); p=0.012], Ct value [OR 0.158; 95% CI (0.025 to 0.987); p=0.048] and PII [OR 1.912; 95% CI (1.187 to 3.079); p=0.008]. Interpretation Three key-independent risk factors of COVID-19 were identified, including age, PII, and Ct value. The Ct value is closely correlated with the severity of COVID-19, and may act as a predictor of clinical severity of COVID-19 in the early stage. SARS-CoV-2 myocarditis should be highlighted despite a relatively low incidence rate (4.8%). The oxygen pressure and blood oxygen saturation should not be neglected as closely linked with the altitude of epidemic regions.

negative: Current status of treatment for 2019 novel coronavirus pneumonia/ 中华微生物学和免疫学杂志 2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.

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: Digit analysis for Covid-19 reported data The coronavirus which appeared in December 2019 in Wuhan has spread out worldwide and caused the death of more than 280,000 people (as of May, 11 2020). Since February 2020, doubts were raised about the numbers of confirmed cases and deaths reported by the Chinese government. In this paper, we examine data available from China at the city and provincial levels and we compare them with Canadian provincial data, US state data and French regional data. We consider cumulative and daily numbers of confirmed cases and deaths and examine these numbers through the lens of their first two digits and in particular we measure departures of these first two digits to the Newcomb-Benford distribution, often used to detect frauds. Our finding is that there is no evidence that cumulative and daily numbers of confirmed cases and deaths for all these countries have different first or second digit distributions. We also show that the Newcomb-Benford distribution cannot be rejected for these data.

negative: Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods

negative: Coronavirus infection of the bovine respiratory tract Abstract Two viruses, morphologically resembling coronaviruses and antigenically indistinguishable from bovine enteric coronavirus, were isolated in bovine tracheal organ cultures from the lungs and trachea of young calves with respiratory disease. Intranasal and intratracheal inoculation of these viruses into neonatal calves resulted in a predominantly upper respiratory tract infection, which was associated with the development of mild respiratory symptoms.

negative: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (≥65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.

negative: The Regulation and Maturation of Antiviral Immune Responses

negative: Mutterschutz  auch im Zeitalter der Coronakrise./ [Maternity protection-also during the corona crisis] Pregnant employees should be protected, particularly in crisis situations. The Maternity Protection Act states that employees are not allowed to have contact with infectious people, including people with SARS-CoV-2 infections; no new regulation is required here.

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: Häusliche Isolation und Quarantäne gut überstehen The novel coronavirus SARS-CoV‑2 and the disease caused by it with the official name coronavirus disease 2019 (COVID-19) is forcing the implementation of drastic measures worldwide, which are aimed at containing the massive spread. The measures include domestic isolation of the population as far as possible. Domestic isolation and quarantine are, however, exceptional situations, which most people have not yet experienced. These set measures can have an effect on the psyche and be very debilitating for those affected. Clear behavioral measures and mental strategies, which have been scientifically researched and established in psychology, help to overcome this exceptional situation.

negative: COVID-19 Docking Server: An interactive server for docking small molecules, peptides and antibodies against potential targets of COVID-19 The coronavirus disease 2019 (COVID-19) caused by a new type of coronavirus has been emerging from China and led to thousands of death globally since December 2019. Despite many groups have engaged in studying the newly emerged virus and searching for the treatment of COVID-19, the understanding of the COVID-19 target -ligand interactions represents a key challenge. Herein, we introduce COVID-19 Docking Server, a web server that predicts the binding modes between COVID-19 targets and the ligands including small molecules, peptide and antibody. Structures of proteins involved in the virus life cycle were collected or constructed based on the homologs of coronavirus, and prepared ready for docking. The platform provides a free and interactive tool for the prediction of COVID-19 target-ligand interactions and following drug discovery for COVID-19.

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: Management of the dead during COVID-19 outbreak in Malaysia The emergence of a novel human coronavirus, SARS-CoV-2, causing severe respiratory tract infections in humans, is affecting all countries of the world and has become a global health concern. Since the virus was first identified in December 2019, the number of deaths have been propagating exponentially, causing countries across the world, including Malaysia, to increase emergency measures to combat the virus. Due to the fact that the COVID-19 pandemic does not discriminate its victims, it is of paramount importance to construct a plan for management of the dead for all suspected or confirmed COVID-19 cases, including the unidentified deceased, as an essential portion of the humanitarian forensic action approach. This document provides an overview on ways to maximize the local collective capacity from various government agencies to manage the dead based on the prevailing regulations and legislation in the country, in preparation for possible large scale deaths from this pandemic. The National Institute of Forensic Medicine Malaysia has improvised procedures and guidelines for management of the dead within the existing regulations in order to achieve a balance between medicolegal requirements and the safety of personnel managing the bodies of the deceased with suspected or confirmed COVID-19 infection; at the site of death, during transport, during postmortem procedures, storage and preparation before and during burial or cremation as well as environmental cleaning and disinfection, involving various agencies in the country. A form of temporary controlled burial is as an option to allow the reinvestigation of a decedent to help formally identify victims of the pandemic such as undocumented migrants or refugees who were previously not identified. Due to the different legal requirements and mortality rates between countries, there is no one-size-fits-all approach to the management of the dead. Whenever possible, every opportunity and assistance must be given to families to mourn their loved ones, even in times of crisis or an outbreak, in order to sustain an appropriate level of dignity and respect.

negative: In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.

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: How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015–2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID–19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.

negative: Tomar medidas preventivas inmediatamente: evidencia de China sobre el COVID-19

negative: Management of Patients on Dialysis and With Kidney Transplantation During the SARS-CoV-2 (COVID-19) Pandemic in Brescia, Italy The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7–10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management.

negative: “Differential risk of hospitalization among single virus infections causing influenza‐like illnesses” BACKGROUND: Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI). METHODS: Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza. RESULTS: A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively). CONCLUSIONS: Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.

negative: Why are pregnant women susceptible to COVID-19? An immunological viewpoint Abstract The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.

negative: Investigating the Impact of Asymptomatic Carriers on COVID-19 Transmission Coronavirus disease 2019 (COVID-19) is a novel human respiratory disease caused by the SARS-CoV-2 virus. Asymptomatic carriers of the virus display no clinical symptoms but are known to be contagious. Recent evidence reveals that this sub-population, as well as persons with mild, represent a major contributor in the propagation of COVID-19. The asymptomatic sub-population frequently escapes detection by public health surveillance systems. Because of this, the currently accepted estimates of the basic reproduction number (Ro) of the virus are inaccurate. It is unlikely that a pathogen can blanket the planet in three months with an Ro in the vicinity of 3, as reported in the literature. In this manuscript, we present a mathematical model taking into account asymptomatic carriers. Our results indicate that an initial value of the effective reproduction number could range from 5.5 to 25.4, with a point estimate of 15.4, assuming mean parameters. The first three weeks of the model exhibit exponential growth, which is in agreement with average case data collected from thirteen countries with universal health care and robust communicable disease surveillance systems; the average rate of growth in the number of reported cases is 23.3% per day during this period.

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: MERS coronavirus outbreak: Implications for emerging viral infections Abstract In September 2012, a novel coronavirus was isolated from a patient who died in Saudi Arabia after presenting with acute respiratory distress and acute kidney injury. Analysis revealed the disease to be due to a novel virus which was named Middle East Respiratory Coronavirus (MERS-CoV). There have been several MERS-CoV hospital outbreaks in KSA, continuing to the present day, and the disease has a mortality rate in excess of 35%. Since 2012, the World Health Organization has been informed of 2220 laboratory-confirmed cases resulting in at least 790 deaths. Cases have since arisen in 27 countries, including an outbreak in the Republic of Korea in 2015 in which 36 people died, but more than 80% of cases have occurred in Saudi Arabia.. Human-to-human transmission of MERS-CoV, particularly in healthcare settings, initially caused a ‘media panic’, however human-to-human transmission appears to require close contact and thus far the virus has not achieved epidemic potential. Zoonotic transmission is of significant importance and evidence is growing implicating the dromedary camel as the major animal host in spread of disease to humans. MERS-CoV is now included on the WHO list of priority blueprint diseases for which there which is an urgent need for accelerated research and development as they have the potential to cause a public health emergency while there is an absence of efficacious drugs and/or vaccines. In this review we highlight epidemiological, clinical, and infection control aspects of MERS-CoV as informed by the Saudi experience. Attention is given to recommended treatments and progress towards vaccine development.

negative: What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective

negative: Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20–83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

negative: Effects of air temperature and relative humidity on coronavirus survival on surfaces. Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.

negative: Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonosis that causes death in 35·7% of cases. As of Feb 28, 2018, 2182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide, with most being reported in Saudi Arabia (1807 cases with 705 deaths). MERS-CoV features prominently in the WHO blueprint list of priority pathogens that threaten global health security. Although primary transmission of MERS-CoV to human beings is linked to exposure to dromedary camels (Camelus dromedarius), the exact mode by which MERS-CoV infection is acquired remains undefined. Up to 50% of MERS-CoV cases in Saudi Arabia have been classified as secondary, occurring from human-to-human transmission through contact with asymptomatic or symptomatic individuals infected with MERS-CoV. Hospital outbreaks of MERS-CoV are a hallmark of MERS-CoV infection. The clinical features associated with MERS-CoV infection are not MERS-specific and are similar to other respiratory tract infections. Thus, the diagnosis of MERS can easily be missed, unless the doctor or health-care worker has a high degree of clinical awareness and the patient undergoes specific testing for MERS-CoV. The largest outbreak of MERS-CoV outside the Arabian Peninsula occurred in South Korea in May, 2015, resulting in 186 cases with 38 deaths. This outbreak was caused by a traveller with undiagnosed MERS-CoV infection who became ill after returning to Seoul from a trip to the Middle East. The traveller visited several health facilities in South Korea, transmitting the virus to many other individuals long before a diagnosis was made. With 10 million pilgrims visiting Saudi Arabia each year from 182 countries, watchful surveillance by public health systems, and a high degree of clinical awareness of the possibility of MERS-CoV infection is essential. In this Review, we provide a comprehensive update and synthesis of the latest available data on the epidemiology, determinants, and risk factors of primary, household, and nosocomial transmission of MERS-CoV, and suggest measures to reduce risk of transmission.

negative: COVID-19 will not leave behind refugees and migrants

negative: Critical Care for Severe COVID-19: A Population-based Study from a Province with Low Case-fatality Rate in China Background Data regarding critical care for patients with severe COVID-19 are limited. We aimed to describe and analyse the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. Methods Using data from Sichuan Provincial Department of Health and the population-based multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included from January 16 to March 15, 2020. All patients were followed-up from the day of inclusion, noted as Day one (D1), until discharge, death, or the end of the study. Findings Out of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation. Among the five predefined criteria for severe illness, low PaO2:FiO2 ratio (<300 mmHg) was the most commonly reported, accounting for 87.7% of the severe diagnosed. By establishing provisional ICUs, all 81 patients were admitted to hospitals capable of providing critical care, among whom 51 (63.0%) were treated in provisional ICUs. On D1, 77 patients (95.1%) were admitted, 76 (93.8%) were administered by respiratory support, including 51 (67.9%) by conventional oxygen therapy (COT). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by high-flow nasal cannula (19.5%) and non-invasive mechanical ventilation (10%). Interpretation The multi-strategy management for severe COVID-19 patients included early identification and timely critical care, including appropriate respiratory support in particular. Preparation of sufficient conventional oxygen equipment should be prioritized.

negative: Domestic Pig Unlikely Reservoir for MERS-CoV We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.

negative: Behavioural intentions in response to an influenza pandemic BACKGROUND: Little is known regarding which behavioural responses can be expected if an influenza pandemic were to occur. METHODS: A survey comprising questions based on risk perception theories, in particular PMT, was conducted with a Dutch sample. RESULTS: Although fear that an influenza pandemic may occur was high, participants do not feel well informed. General practitioners and local health authorities were considered trustworthy sources of information and the information considered most urgent pertained to which protective measures should be taken. Participants reported an intention to comply with recommendations regarding protective measures. However, response and self efficacy were low. Maladaptive behaviours can be expected. Increasing numbers of ill individuals and school closures are also expected to lead to a decreased work force. Participants indicated wanting antiviral drugs even if the supply were to be insufficient. CONCLUSIONS: Messages regarding health protective behaviours from local health authorities should anticipate the balance between overreacting and underreacting. Also, when protective recommendations from health professionals conflict with company policies, it is unclear how employees will react.

negative: Recomendaciones sobre el manejo clínico de la infección por el «nuevo coronavirus» SARS-CoV2. Grupo de trabajo de la Asociación Española de Pediatría (AEP) Resumen El 31 de diciembre de 2019, la Comisión Municipal de Salud y Sanidad de Wuhan (provincia de Hubei, China) informó sobre la existencia de 27 casos de neumonía de etiología desconocida con inicio de síntomas el 8 de diciembre, incluyendo 7 casos graves, con exposición común a un mercado de marisco, pescado y animales vivos en la ciudad de Wuhan. El 7 de enero de 2020, las autoridades chinas identificaron como agente causante del brote un nuevo tipo de virus de la familia Coronaviridae, denominado temporalmente «nuevo coronavirus», 2019-nCoV. El 30 de enero de 2020 la Organización Mundial de la Salud (OMS) declara el brote una Emergencia Internacional. El día 11 de febrero la OMS le asigna el nombre de SARS-CoV2 e infección COVID-19 (Coronavirus Infectious Disease). El Ministerio de Sanidad convoca a las Sociedades de Especialidades para la elaboración de un protocolo clínico de manejo de la infección. La Asociación Española de Pediatría nombra un grupo de trabajo de las Sociedades de Infectología Pediátrica y Cuidados Intensivos Pediátricos que se encargan de elaborar las presentes recomendaciones con la evidencia disponible en el momento de su realización. Abstract On 31 December 2019, the Wuhan Municipal Committee of Health and Healthcare (Hubei Province, China) reported that there were 27 cases of pneumonia of unknown origin with symptoms starting on the 8 December. There were 7 serious cases with common exposure in market with shellfish, fish, and live animals, in the city of Wuhan. On 7 January 2020, the Chinese authorities identified that the agent causing the outbreak was a new type of virus of the Coronaviridae family, temporarily called «new coronavirus», 2019-nCoV. On January 30th, 2020, the World Health Organisation (WHO) declared the outbreak an International Emergency. On 11 February 2020 the WHO assigned it the name of SARS-CoV2 and COVID-19 (SARS-CoV2 and COVID-19). The Ministry of Health summoned the Specialties Societies to prepare a clinical protocol for the management of COVID-19. The Spanish Paediatric Association appointed a Working Group of the Societies of Paediatric Infectious Diseases and Paediatric Intensive Care to prepare the present recommendations with the evidence available at the time of preparing them.

negative: Using ICU data to improve the real-time estimation of the effective reproductive number of the COVID-19 epidemic in 9 European countries We replicate a recent study by the Imperial College COVID-19 Response Team (Flaxman et al, 2020) that estimates both the effective reproductive number, Rt, of the current COVID-19 epidemic in 11 European countries, and the impact of different nonpharmaceutical interventions that have been implemented to try to contain the epidemic. We improve on their estimation by using data from the number of patients in intensive care, which provides two advantages over the number of deaths: first, it can be used to construct a signal with less bias: as the healthcare system of a country reaches saturation, the mortality rate would be expected to increase, which would bias the estimates of Rt and of the impact of measures implemented to contain the epidemic; and second, it is a signal with less lag, as the time from onset of symptoms to ICU admission is shorter than the time from onset to death. The intensive care signal we use is not just the number of people in ICU, as this would also be biased if the healthcare system has reached saturation. Instead, we estimate the daily demand of intensive care, as the sum of two components: the part that is satisfied (new ICU admissions) and the part that is not (which results in excess mortality). Thanks to the advantages of this ICU signal in terms of timeliness and bias, we find that most of the countries in the study have already reached Rt<1 with 95% confidence (Italy, Spain, Austria, Denmark, France, Norway and Switzerland, but not Belgium or Sweden), whereas the original methodology of Flaxman et al (2020), even with updated data, would only find Rt<1 with 95% confidence for Italy and Switzerland.

negative: Corona Epidemic in Indian context: Predictive Mathematical Modelling The novel Coronavirus pathogen Covid-19 is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. The virus that first manifested in Wuhan, China has travelled across continents. The increase in number of deaths in Italy, Iran, USA, and other countries has alarmed both the developed and developing countries. Scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. India, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. Health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. The administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. However, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in Indian context. Different states have adopted measures to stop the community spread. Considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. In this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. The data can be used by the health care agencies, the Government Organizations and the Planning Commission to make suitable arrangements to fight the pandemic. Though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. The recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels.

negative: 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.

negative: Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review. BACKGROUND Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with respiratory virus diseases, and are currently being investigated in trials as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19. SEARCH METHODS The protocol was pre-published with the Center for Open Science and can be accessed here: osf.io/dwf53 We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trials registries to identify ongoing studies and results of completed studies on 23 April 2020 for case-series, cohort, prospectively planned, and randomised controlled trials (RCTs). SELECTION CRITERIA We followed standard Cochrane methodology and performed all steps regarding study selection in duplicate by two independent review authors (in contrast to the recommendations of the Cochrane Rapid Reviews Methods Group). We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulins. DATA COLLECTION AND ANALYSIS We followed recommendations of the Cochrane Rapid Reviews Methods Group regarding data extraction and assessment. To assess bias in included studies, we used the assessment criteria tool for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events, and serious adverse events. MAIN RESULTS: We included eight studies (seven case-series, one prospectively planned, single-arm intervention study) with 32 participants, and identified a further 48 ongoing studies evaluating convalescent plasma (47 studies) or hyperimmune immunoglobulin (one study), of which 22 are randomised. Overall risk of bias of the eight included studies was high, due to: study design; small number of participants; poor reporting within studies; and varied type of participants with different severities of disease, comorbidities, and types of previous or concurrent treatments, including antivirals, antifungals or antibiotics, corticosteroids, hydroxychloroquine and respiratory support. We rated all outcomes as very low certainty, and we were unable to summarise numerical data in any meaningful way. As we identified case-series studies only, we reported results narratively. Effectiveness of convalescent plasma for people with COVID-19 The following reported outcomes could all be related to the underlying natural history of the disease or other concomitant treatment, rather than convalescent plasma. All-cause mortality at hospital discharge All studies reported mortality. All participants were alive at the end of the reporting period, but not all participants had been discharged from hospital by the end of the study (15 participants discharged, 6 still hospitalised, 11 unclear). Follow-up ranged from 3 days to 37 days post-transfusion. We do not know whether convalescent plasma therapy affects mortality (very low-certainty evidence). Improvement of clinical symptoms (assessed by respiratory support) Six studies, including 28 participants, reported the level of respiratory support required; most participants required respiratory support at baseline. All studies reported improvement in clinical symptoms in at least some participants. We do not know whether convalescent plasma improves clinical symptoms (very low-certainty evidence). Time to discharge from hospital Six studies reported time to discharge from hospital for at least some participants, which ranged from four to 35 days after convalescent plasma therapy. Admission on the intensive care unit (ICU) Six studies included patients who were critically ill. At final follow-up the majority of these patients were no longer on the ICU or no longer required mechanical ventilation. Length of stay on the ICU Only one study (1 participant) reported length of stay on the ICU. The individual was discharged from the ICU 11 days after plasma transfusion. Safety of convalescent plasma for people with COVID-19 Grade 3 or 4 adverse events The studies did not report the grade of adverse events after convalescent plasma transfusion. Two studies reported data relating to participants who had experienced adverse events, that were presumably grade 3 or 4. One case study reported a participant who had moderate fever (38.9 °C). Another study (3 participants) reported a case of severe anaphylactic shock. Four studies reported the absence of moderate or severe adverse events (19 participants). We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence). Serious adverse events One study (3 participants) reported one serious adverse event. As described above, this individual had severe anaphylactic shock after receiving convalescent plasma. Six studies reported that no serious adverse events occurred. We are very uncertain whether or not convalescent plasma therapy affects the risk of serious adverse events (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified eight studies (seven case-series and one prospectively planned single-arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID-19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low-certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID-19; all studies were at high risk of bias and reporting quality was low. No RCTs or controlled non-randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here.

negative: New threat: 2019 novel Coronavirus infection and infection control perspective in Turkey

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: Acute kidney injury in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study Background: The kidney may be affected in coronavirus-2019 disease (COVID-19). This study assessed the predictors and outcomes of acute kidney injury (AKI) among individuals with COVID-19. Methods: This observational study, included data on all patients with clinically confirmed COVID-19 admitted to Hankou Hospital, Wuhan, China from January 5 to March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was censored on March 8, 2020. This is a single-center, retrospective, observational study. Patients clinically confirmed COVID-19 and admitted to Hankou Hospital, Wuhan, China from January 5 to March 8, 2020 were enrolled. We evaluated the association between changes in the incidence of AKI and COVID-19 disease and clinical outcomes by using logistic regression models. Results: A total of 287 patients, 55 with AKI and 232 without AKI, were included in the analysis. Compared to patients without AKI, AKI patients were older, predominantly male, and were more likely to present with hypoxia and have pre-existing hypertension and cerebrovascular disease. Moreover, AKI patients had higher levels of white blood cells, D-dimer, aspartate aminotransferase, total bilirubin, creatine kinase, lactate dehydrogenase, procalcitonin, C-reactive protein, a higher prevalence of hyperkalemia, lower lymphocyte counts, and higher chest computed tomographic scores. The incidence of stage 1 AKI was 14.3%, and the incidence of stage 2 or 3 AKI was 4.9%. Patients with AKI had substantially higher mortality. Conclusions: AKI is an important complication of COVID-19. Older age, male, multiple pre-existing comorbidities, lymphopenia, increased infection indicators, elevated D-dimer, and impaired heart and liver functions were the risk factors of AKI. AKI patients who progressed to stages 2 or 3 AKI had a higher mortality rate. Prevention of AKI and monitoring of kidney function is very important for COVID 19 patients.

negative: A framework for capturing the interactions between laypersons’ understanding of disease, information gathering behaviors, and actions taken during an epidemic Abstract This paper provides a description of a methodological framework designed to capture the inter-relationships between the lay publics’ understanding of health-related processes, information gathering behaviors, and actions taken during an outbreak. We developed and refined our methods during a study involving eight participants living in severe acute respiratory syndrome (SARS)-affected areas (Hong Kong, Taiwan, and Toronto). The framework is an adaptation of narrative analysis, a qualitative method that is used to investigate a phenomenon through interpretation of the stories people tell about their experiences. From our work, several hypotheses emerged that will contribute to future research. For example, our findings showed that many decisions in an epidemic are carefully considered and involve use of significant information gathering. Having a good model of lay actions based on information received and beliefs held will contribute to the development of more effective information support systems in the event of a future epidemic.

negative: A mathematical model for the coronavirus COVID-19 outbreak A mathematical model is proposed for quantitative description of the outbreak of novel coronavirus COVID-19 in China. Although the model is relatively simple, the comparison with the public data shows that an exact solution solution of the model (with the correctly-specified parameters) leads to the results, which are in good agreement with the measured data. Prediction of the total number of the COVID-19 cases is discussed and an example is presented using the measured data in Austria.

negative: Understanding of guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by CAAM Abstract At present, the situation of global fight against COVID-19 is serious. WHO (World Health Organization)-China Joint Mission fully confirms the success of “China's model” against COVID-19 in the report. In fact, one particular power in “China's model” is acupuncture and moxibustion of traditional Chinese medicine. To better apply “non-pharmaceutic measures”—the external technique of traditional Chinese medicine, in the article, the main content of Guidance for acupuncture and moxibustion interventions on COVID-19 (Second edition) issued by China Association of Acupuncture–Moxibution is introduced and the discussion is stressed on the selection of moxibustion device and the duration of its exertion.

negative: Inferring the number of COVID-19 cases from recently reported deaths We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.

negative: Hydroxychloroquine for Covid-19 - When the pandemic runs faster than research

negative: Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (≥65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.

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: Extensions of the SEIR Model for the Analysis of Tailored Social Distancing and Tracing Approaches to Cope with COVID-19 In the context of the COVID-19 pandemic, governments worldwide face the challenge of designing tailored measures of epidemic control to provide reliable health protection while allowing more societal and economic activity. In this paper, we propose an extension of the epidemiological SEIR model to enable a detailed analysis of commonly discussed tailored measures of epidemic control - among them group-specific protection and the use of tracing apps. We introduce groups into the SEIR model that may differ both, in their underlying parameters as well as in their behavioral response to public health interventions. We allow for different infectiousness parameters within and across groups, different asymptomatic, hospitalization, and lethality rates, as well as different take-up rates of tracing apps. Our results visualize the sharp trade-offs between different goals of epidemic control, namely a low death toll, avoiding overload of the health system, and a short duration of the epidemic. We show that a combination of tailored mechanisms, e.g., the protection of vulnerable groups together with a “trace & isolate” approach, can be effective in preventing a high death toll. Protection of vulnerable groups without further measures requires unrealistically strict isolation. A key insight is that high compliance is critical for the effectiveness of a “trace & isolate” approach. Our model allows to analyze the interplay of group-specific social distancing and tracing also beyond our case study in scenarios with a large number of groups reflecting, e.g., sectoral, regional, or age differentiation and group-specific take-up rates for tracing apps.

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: Model studies on the COVID-19 pandemic in Sweden We study the increases of infections and deaths in Sweden caused by COVID-19 with several different models: Firstly an analytical susceptible-infected (SI) model and the standard susceptible-infected-recovered (SIR) model. Then within the SIR framework we study the susceptible-infected-deceased (SID) correlations. All models reproduce well the number of infected cases and give similar predictions. What causes us deep concern is the large number of deaths projected by the SI and SID models. Our analysis shows that, irrespective of the possible uncertainty of our model prediction, the next few days can be critical for determining the future evolution of the death cases (Updated April 02).

negative: COVID-19 Outbreak: An Overview BACKGROUND: In late December 2019, Chinese health authorities reported an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province. SUMMARY: A few days later, the genome of a novel coronavirus was released (http://virological.org/t/novel-2019-coronavirus-genome/319; Wuhan-Hu-1, GenBank accession No. MN908947) and made publicly available to the scientific community. This novel coronavirus was provisionally named 2019-nCoV, now SARS-CoV-2 according to the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. SARS-CoV-2 belongs to the Coronaviridae family, Betacoronavirus genus, subgenus Sarbecovirus. Since its discovery, the virus has spread globally, causing thousands of deaths and having an enormous impact on our health systems and economies. In this review, we summarize the current knowledge about the epidemiology, phylogenesis, homology modeling, and molecular diagnostics of SARS-CoV-2. KEY MESSAGES: Phylogenetic analysis is essential to understand viral evolution, whereas homology modeling is important for vaccine strategies and therapies. Highly sensitive and specific diagnostic assays are key to case identification, contact tracing, identification of the animal source, and implementation of control measures.

negative: How Should the Rehabilitation Community Prepare for 2019-nCoV? Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world’s population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures.

negative: COVID-19 is an emergent disease of aging COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is highly contagious and often leads to severe viral pneumonia with respiratory failure and death in the elderly and subjects with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.

negative: Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis Abstract Background An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 and triggered a Public Health Emergency of International Concern (PHEIC). We aimed to find risk factors for the progression of COVID-19 to help reducing the risk of critical illness and death for clinical help. Methods The data of COVID-19 patients until March 20, 2020 were retrieved from four databases. We statistically analyzed the risk factors of critical/mortal and non-critical COVID-19 patients with meta-analysis. Results Thirteen studies were included in Meta-analysis, including a total number of 3027 patients with SARS-CoV-2 infection. Male, older than 65, and smoking were risk factors for disease progression in patients with COVID-19 (male: OR = 1.76, 95% CI (1.41, 2.18), P < 0.00001; age over 65 years old: OR =6.06, 95% CI(3.98, 9.22), P < 0.00001; current smoking: OR =2.51, 95% CI(1.39, 3.32), P = 0.0006). The proportion of underlying diseases such as hypertension, diabetes, cardiovascular disease, and respiratory disease were statistically significant higher in critical/mortal patients compared to the non-critical patients (diabetes: OR=3.68, 95% CI (2.68, 5.03), P < 0.00001; hypertension: OR = 2.72, 95% CI (1.60,4.64), P = 0.0002; cardiovascular disease: OR = 5.19, 95% CI(3.25, 8.29), P < 0.00001; respiratory disease: OR = 5.15, 95% CI(2.51, 10.57), P < 0.00001). Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease [fever: 0R = 0.56, 95% CI (0.38, 0.82), P = 0.003;shortness of breath or dyspnea: 0R=4.16, 95% CI (3.13, 5.53), P < 0.00001]. Laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/L, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5ng/mL, lactatede hydrogenase(LDH) > 245U/L, and D-dimer > 0.5mg/L predicted the deterioration of disease while white blood cells(WBC)<4 × 109/L meant a better clinical status[AST > 40U/L:OR=4.00, 95% CI (2.46, 6.52), P < 0.00001; Cr ≥ 133μmol/L: OR = 5.30, 95% CI (2.19, 12.83), P = 0.0002; hs-cTnI > 28 pg/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; PCT > 0.5 ng/mL: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001;LDH > 245U/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; D-dimer > 0.5mg/L: OR = 43.24, 95% CI (9.92, 188.49), P < 0.00001; WBC < 4 × 109/L: OR = 0.30, 95% CI (0.17, 0.51), P < 0.00001]. Conclusion Male, aged over 65, smoking patients might face a greater risk of developing into the critical or mortal condition and the comorbidities such as hypertension, diabetes, cardiovascular disease, and respiratory diseases could also greatly affect the prognosis of the COVID-19. Clinical manifestation such as fever, shortness of breath or dyspnea and laboratory examination such as WBC, AST, Cr, PCT, LDH, hs-cTnI and D-dimer could imply the progression of COVID-19.

negative: Impact of population mask wearing on Covid-19 post lockdown COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.

negative: 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

negative: Safeguarding the Maintenance Hemodialysis Patient Population during the Coronavirus Disease 19 Pandemic The World Health Organization has recognized the pandemic nature of the coronavirus disease 19 (COVID-19) outbreak. A large proportion of positive patients require hospitalization, while 5-6% of them may need more aggressive therapies in intensive care. Most governments have recommended social separation and severe measures of prevention of further spreading of the epidemic. Because hemodialysis (HD) patients need to access hospital and dialysis center facilities 3 times a week, this category of patients requires special attention. In this editorial, we tried to summarize the experience of our centers that hopefully may contribute to help other centers and colleagues that are facing the coming wave of the epidemic. Special algorithms for COVID-19 spreading in the dialysis population, recommendations for isolation and preventive measures in positive HD patients, and finally directions to manage logistics and personnel are reported. These recommendations should be considered neither universal nor absolute. Instead, they require local adjustments based on geographic location, cultural and social environments, and level of available resources.

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: Bird Flu, SARS and Beyond In the politically sensitive year of 1997, Hong Kong experienced an outbreak of avian flu when the deadly H5N1 virus unprecedentedly jumped the species barrier from chickens and infected human beings. Hong Kong decided to slaughter over a million chickens, and the virus was stopped in its tracks. In 2003, Hong Kong was the epicenter of the SARS pandemic, which originated in Guangdong province. The Faculty of Medicine played key roles in both instances, with its Microbiology Department successfully identifying a novel coronavirus as being responsible for SARS. Hong Kong learned from its experience and took action to combat the emergence of new infectious diseases. Such vigilance paid off in 2009, when swine flu swept the world, and in 2013, when a novel avian flu H7N9 emerged in China.

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: Microbial challenge studies—a challenge worth accepting

negative: What are our health expectations in a pandemic?

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: [Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]. Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.

negative: Docking study of chloroquine and hydroxychloroquine interaction with RNA binding domain of nucleocapsid phospho-protein - an in silico insight into the comparative efficacy of repurposing antiviral drugs Recent outbreak of novel Coronavirus disease () pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and its N terminal domain (NTD) of Nucleocapsid protein (N protein) binds to the viral (+) sense RNA and results in virus ribonucleoprotien complex, essential for the virus replication. The N protein is composed of a serine-rich linker region sandwiched between NTD and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. Therefore, there is always a quest to target RNA binding domain of nucleocapsid phosphoprotein (NTD-N-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the NTD-N-protein of SARS-CoV-2. With the help of various computational methods, we have explored the potential role of both of these antiviral drugs for the treatment of patients by comparing the efficacy of both of the drugs to bind to NTD-N-protein. In our research Hydroxychloroquine exhibited potential inhibitory effects of NTD-N-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with . Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with . We further hypothesize that the comparative NTD-N-protein -drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.Communicated by Ramaswamy H. Sarma.

negative: STEMI care during COVID-19: losing sight of the forest for the trees [Figure: see text]

negative: Novel Corona virus Disease infection in Tunisia: Mathematical model and the impact of the quarantine strategy In this paper, we propose a new model for the dynamics of COVID-19 infections. Our approach consists of seven phenotypes: the susceptible humans, exposed humans, infectious humans, the recovered humans, the quarantine population, the recovered-exposed and deceased population. We proved first through mathematical approach the positivity, boundness and existence of a solution to considered model. We also studied the existence of the disease free equilibrium and corresp onding stability. Hence, the actual reproduction number was calculated . We analyzed the dependence of basic reproductions R_0 on the confidence of our model. Our work shows, in particular, that the disease will decrease out if the number of reproduction was less than one. Moreover, the impact of the quarantine strategies to reduce the spread of this disease is discussed. The theoretical results are validated by some numerical simulations of the system of the epidemic's differential equations.

negative: Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.

negative: Noninvasive ventilation in acute respiratory failure due to H1N1 influenza: A word of caution

negative: Inactivating influenza viruses on surfaces using hydrogen peroxide or triethylene glycol at low vapor concentrations BACKGROUND: Surfaces in congregate settings, such as vehicles used for mass transportation, can become contaminated with infectious microorganisms and facilitate disease transmission. We disinfected surfaces contaminated with H1N1 influenza viruses using hydrogen peroxide (HP) vapor at concentrations below 100 ppm and triethylene glycol (TEG)-saturated air containing 2 ppm of TEG at 25°C. METHODS: Influenza viruses in aqueous suspensions were deposited on stainless-steel coupons, allowed to dry at ambient conditions, and then exposed for up to 15 minutes to 10 to 90 ppm of HP vapor or TEG-saturated air. Virus assays were done on the solution used to wash the viruses from these coupons and from coupons treated similarly but without exposure to HP or TEG vapor. RESULTS: After 2.5 minutes, exposure to 10-ppm HP vapor resulted in 99% inactivation. For air saturated with TEG at 25 to 29°C, the disinfection rate was about 1.3 log(10) reductions per hour, about 16 times faster than the measured natural inactivation rate under ambient conditions. CONCLUSIONS: Vapor concentrations of 10 ppm HP or 2 ppm TEG can provide effective surface disinfection. At these low concentrations, the potential for damage to even the avionics of an airplane would be expected to be minimal. At a TEG vapor concentration of 2 ppm, there are essentially no health risks to people.

negative: Prevalence of diabetes mellitus in 2019 novel coronavirus: a Meta-analysis Abstract Background Since December 2019, a new strain ofcoronavirus named 2019 novel coronavirus (2019-nCoV) has been discovered in Wuhan. The prevalence of diabetes mellitus, which is a great public health issue leading to immunity inhibition and anincreased incidenceofinfections, has been increasing over the past ten years. The aim of this research was to systematically assess the prevalence of diabetes mellitus among 2019-nCoV. Methods We searched PubMed, Embase, Web of Science and Medline for observational studies up to February 25, 2020. A random effects model or fixed-effects model was applied to evaluate the pooled prevalence of diabetes mellitus and odds ratio (OR) with 95% confidence interval (CI). Findings In total, nine papers met the eligibility criteria. The pooled prevalence of DM was 9% (95% CI 6%–12%). There was obvious heterogeneity (I2 65%, p=0.004) in the prevalence of DM in these studies. The prevalence of DM in moderate patients with 2019-nCoV was 7% (95% CI 4%–10%). The prevalence of DM in severe patients with 2019-nCoV was 17% (95% CI 13%–21%). The prevalence of DM in severe patients with 2019-nCoV was significantly higher than that in moderate patients with 2019-nCoV (OR 2.49, 95% CI 1.70 to 3.64). Interpretation To our knowledge, this work is the first report showing the prevalence of diabetes mellitus in patients with 2019-nCoV, which is beneficial to prevent the spread of 2019-nCoV in the future.

negative: Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID‐19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R(0)) of COVID‐19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.

negative: SARS to novel coronavirus – old lessons and new lessons The response to the novel coronavirus outbreak in China suggests that many of the lessons from the 2003 SARS epidemic have been implemented and the response improved as a consequence. Nevertheless some questions remain and not all lessons have been successful. The national and international response demonstrates the complex link between public health, science and politics when an outbreak threatens to impact on global economies and reputations. The unprecedented measures implemented in China are a bold attempt to control the outbreak – we need to understand their effectiveness to balance costs and benefits for similar events in the future.

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: Intravenous Vitamin C for reduction of cytokines storm in Acute Respiratory Distress Syndrome Abstract The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specifically address the cytokines' storm characteristic of the Acute Respiratory Distress Syndrome (ARDS) that occur in the later cycle of the Covid19 infectious disease.

negative: Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (2019 coronavirus disease, COVID-19) since December 2019, from Wuhan, China, has been posing a significant threat to global human health. The clinical features and outcomes of Chinese patients with COVID-19 have been widely reported. Increasing evidence has witnessed the frequent incident liver injury in COVID-19 patients, and it is often manifested as transient elevation of serum aminotransferases; however, the patients seldom have liver failure and obvious intrahepatic cholestasis, unless pre-existing advanced liver disease was present. The underlying mechanisms of liver injury in cases of COVID-19 might include psychological stress, systemic inflammation response, drug toxicity, and progression of pre-existing liver diseases. However, there is insufficient evidence for SARS-CoV-2 infected hepatocytes or virus-related liver injury in COVID-19 at present. The clinical, pathological and laboratory characteristics as well as underlying pathophysiology and etiology of liver injury in COVID-19 remain largely unclear. In this review, we highlight these important issues based on the recent developments in the field, for optimizing the management and treatment of liver injury in Chinese patients with COVID-19.

negative: Concerns for activated breathing control (ABC) with breast cancer in the era of COVID-19: Maximizing infection control while minimizing heart dose

negative: TRACKing Excess Deaths (TRACKED): an interactive online tool to monitor excess deaths associated with COVID-19 pandemic in the United Kingdom Aim: We aimed to describe trends of excess mortality in the United Kingdom (UK) stratified by nation and cause of death, and to develop an online tool for reporting the most up to date data on excess mortality. Methods: Population statistics agencies in the UK including the Office for National Statistics (ONS), National Records of Scotland (NRS), and Northern Ireland Statistics and Research Agency (NISRA) publish weekly data on deaths. We used mortality data up to 22nd May in the ONS and the NISRA and 24th May in the NRS. Crude mortality for non-COVID deaths (where there is no mention of COVID-19 on the death certificate) calculated. Excess mortality defined as difference between observed mortality and expected average of mortality from previous 5 years. Results: There were 56,961 excess deaths and 8,986 were non-COVID excess deaths. England had the highest number of excess deaths per 100,000 population (85) and Northern Ireland the lowest (34). Non-COVID mortality increased from 23rd March and returned to the 5-year average on 10th May. In Scotland, where underlying cause mortality data besides COVID-related deaths was available, the percentage excess over the 8-week period when COVID-related mortality peaked was: dementia 49%, other causes 21%, circulatory diseases 10%, and cancer 5%. We developed an online tool (TRACKing Excess Deaths - TRACKED) to allow dynamic exploration and visualisation of the latest mortality trends. Conclusions: Continuous monitoring of excess mortality trends and further integration of age- and gender-stratified and underlying cause of death data beyond COVID-19 will allow dynamic assessment of the impacts of indirect and direct mortality of the COVID-19 pandemic.

negative: Vorbereitung des Einsatzes Für den Einsatz eines Bauleiters ist es besonders wichtig, sich auf seine Rolle vorzubereiten, die dazu erforderlichen Vollmachten abzufordern und alle Möglichkeiten der persönlichen Einsatzvorbereitung zu kennen und landesspezifisch zu nutzen. Im Vergleich zum Inlandeinsatz ergeben sich dabei bedeutend höhere Anforderungen für die späteren Aufgaben.

negative: Coping with diabetes during the COVID – 19 lockdown in India: Results of an online pilot survey AIM: The management of diabetes has become a challenge due to the COVID 19 lockdown. An online-based pilot survey was conducted to study how people with diabetes were coping with their Diabetes during the COVID - 19 lockdown. METHOD: The questions were designed in an online survey, Survey Monkey, to conduct this cross-sectional study. The link was generated and sent to 100 registered patients of the MV Hospital for Diabetes Royapuram who had not contacted the hospital after the lockdown announcement. The survey was done between April 1 and April 15, 2020.Oral consent was obtained through telephone before the link was sent by Whatsapp to them.The questionnaire consisted of questions on home blood glucose monitoring, regularity in doing their physical activity and dietary compliance and anxiety about the viral infection. RESULTS: 92% of the participants had Type 2 diabetes. Only 28% of the participants were checking their blood glucose levels regularly. 80% of the participants mentioned that they were following regular exercise and diet control during the lockdown period. 40% of the participants were anxious about the Covid infection. CONCLUSION: SMBG needs to be practiced on regular basis, especially among the patients with diabetes on insulin therapy. Most of the people surveyed were coping well with their Diabetes. Patients have reported that they were able to maintain proper dietary compliance and be more physically active at home during this lockdown. These findings need to be ascertained in larger sample of patients.

negative: Sex difference and smoking predisposition in patients with COVID-19

negative: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.

negative: Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

negative: Gender differences in patients with COVID-19: a narrative review. In December 2019 a novel coronavirus emerged in Wuhan, China causing many cases of severe pneumonia. World Health Organization (WHO) named this disease Coronavirus Disease 2019 (COVID-19). The infection has rapidly spread across China to many other countries, and on March 12, 2020 the WHO declared pandemic outbreak of COVID-19. As of May 16, 2020, COVID-19 has been diagnosed in more than 4,490,000 patients, associated to 305,976 deaths worldwide; in Italy 224,760 COVID-19 cases have been reported with 31,763 deaths. The main routes of transmission are respiratory droplets and direct contact with infected people, so numerous prevention strategies are employed to mitigate the spread of disease, including social distancing and isolation. The aim of this narrative review is to underline gender differences in epidemiology, etiopathogenesis, risk factors, clinical presentation, diagnosis, prognosis and mortality of patients infected with SARS-CoV-2. Currently data on the sex indicators for admitted or deceased patients are only available, but there is no analysis about other gender indicators. The data considered in our study are the only currently available in the literature, but it is appropriate to implement a specific analysis with all gender indicators to identify appropriate strategies. Moreover, the evaluation of a health service efficiency is a key element to define gender outcomes. Knowing the gender differences in COVID-19 outbreak would be a fundamental tool to understand the effects of a health emergency on individuals and communities as well as to carry out effective and equitable policies, public health measures and targeted solutions.

negative: Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis We perform a counterfactual time series analysis using two different Data Science methods applied to 2020 mortality data reported from towns in Italy, with data from the previous five years as control. We find an excess mortality that is correlated in time with the COVID-19 reported death rate time series. Our analysis shows good agreement with reported COVID-19 mortality for age<70 years, but an excess in total mortality increasing with age above 70 years, suggesting there is a large population of predominantly old people missing from the official fatality statistics. We estimate that the number of COVID-19 deaths in Italy is 52,000 ± 2000 as of April 18 2020, more than a factor of 2 higher than the official number. The Population Fatality Rate (PFR) has reached 0.22% in the most affected region of Lombardia and 0.57% in the most affected province of Bergamo,which constitutes a lower bound to the Infection Fatality Rate (IFR). We estimate PFR as a function of age, finding a steep age dependence: in Lombardia (Bergamo province) 0.6% (1.7%) of the total population in age group 70-79 died, 1.6% (4.6%) in age group 80-89, and 3.41% (10.2%) in the age group above 90. We combine this with the Test Positivity Rate to estimate the lower bound of 0.84% on the IFR for Lombardia. We observe IFR to trace the Yearly Mortality Rate (YMR) above 60 years, which can be used to estimate the IFR for other regions in the world. We predict an IFR lower bound of 0.5% for NYC and 26% of total COVID-19 mortality arising from the population below 65 years, in agreement with the existing data and several times higher than Lombardia. Combining PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates(IR) of regions in Italy, which peak in Lombardia at 23% (12%-41%, 95% c.l.), and for provinces in Bergamo at 67% (33%-100%, 95% c.l.). This suggests that Bergamo may have reached herd immunity, and that the number of infected people greatly exceeds the number of positive tests, by a factor of 35 in Lombardia.

negative: A Multicenter Consortium to Define the Epidemiology and Outcomes of Pediatric Solid Organ Transplant Recipients With Inpatient Respiratory Virus Infection BACKGROUND: Respiratory virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear. METHODS: A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant. An RVI diagnosis required respiratory symptoms and detection of a virus (ie, human rhinovirus/enterovirus, human metapneumovirus, influenza virus, parainfluenza virus, coronavirus, and/or respiratory syncytial virus). The incidence of RVI was calculated, and the association of baseline SOT factors with subsequent pulmonary complications and death was assessed. RESULTS: Of 1096 pediatric SOT recipients (448 liver, 289 kidney, 251 heart, 66 lung, 42 intestine/multivisceral), 159 (14.5%) developed RVI associated with hospitalization within 12 months after their transplant. RVI occurred at the highest rates in intestine/abdominal multivisceral (38%), thoracic (heart/lung) (18.6%), and liver (15.6%) transplant recipients and a lower rate in kidney (5.5%) transplant recipients. RVI was associated with younger median age at transplant (1.72 vs 7.89 years; P < .001) and among liver or kidney transplant recipients with the receipt of a deceased-donor graft compared to a living donor (P = .01). The all-cause and attributable case-fatality rates within 3 months of RVI onset were 4% and 0%, respectively. Multivariable logistic regression models revealed that age was independently associated with increased risk for a pulmonary complication (odds ratio, 1.24 [95% confidence interval, 1.02–1.51]) and that receipt of an intestine/multivisceral transplant was associated with increased risk of all-cause death (odds ratio, 24.54 [95% confidence interval, 1.69–327.96]). CONCLUSIONS: In this study, hospital-associated RVI was common in the first year after pediatric SOT and associated with younger age at transplant. All-cause death after RVI was rare, and no definitive attributable death occurred.

negative: A demographic scaling model for estimating the total number of COVID-19 infections Understanding how widely COVID-19 has spread is critical for examining the pandemic's progression. Despite efforts to carefully monitor the pandemic, the number of confirmed cases may underestimate the total number of infections. We introduce a demographic scaling model to estimate COVID-19 infections using an broadly applicable approach that is based on minimal data requirements: COVID-19 related deaths, infection fatality rates (IFRs), and life tables. As many countries lack reliable estimates of age-specific IFRs, we scale IFRs between countries using remaining life expectancy as a marker to account for differences in age structures, health conditions, and medical services. Across 10 countries with most COVID-19 deaths as of May 13, 2020, the number of infections is estimated to be four [95% prediction interval: 2-11] times higher than the number of confirmed cases. Cross-country variation is high. The estimated number of infections is 1.4 million (six times the number of confirmed cases) for Italy; 3.1 million (2.2 times the number of confirmed cases) for the U.S.; and 1.8 times the number of confirmed cases for Germany, where testing has been comparatively extensive. Our prevalence estimates, however, are markedly lower than most others based on local seroprevalence studies. We introduce formulas for quantifying the bias that is required in our data on deaths in order to reproduce estimates published elsewhere. This bias analysis shows that either COVID-19 deaths are severely underestimated, by a factor of two or more; or alternatively, the seroprevalence based results are overestimates and not representative for the total population.

negative: Chemical disinfection of non-porous inanimate surfaces experimentally contaminated with four human pathogenic viruses. The chemical disinfection of virus-contaminated non-porous inanimate surfaces was investigated using coxsackievirus B3, adenovirus type 5, parainfluenza virus type 3 and coronavirus 229E as representatives of important nosocomial viral pathogens. A 10 microliter amount of the test virus, suspended in either faeces or mucin, was placed onto each stainless steel disk (about 1 cm in diameter) and the inoculum allowed to dry for 1 h under ambient conditions. Sixteen disinfectant formulations were selected for this study based on the findings of an earlier investigation with a human rotavirus. After 1 min exposure to 20 microliters of the disinfectant, the virus from the disks was immediately eluted into tryptose phosphate broth and plaque assayed. Using an efficacy criterion of a 3 log10 or greater reduction in virus infectivity titre and irrespective of the virus suspending medium, only the following five disinfectants proved to be effective against all the four viruses tested: (1) 2% glutaraldehyde normally used as an instrument soak, (2) a strongly alkaline mixture of 0.5% sodium o-benzyl-p-chlorophenate and 0.6% sodium lauryl sulphate, generally used as a domestic disinfectant cleaner for hard surfaces, (3) a 0.04% solution of a quaternary ammonium compound containing 7% hydrochloric acid, which is the basis of many toilet bowl cleaners, (4) chloramine T at a minimum free chlorine level of 3000 p.p.m. and (5) sodium hypochlorite at a minimum free chlorine concentration of 5000 p.p.m. Of those chemicals suitable for use as topical antiseptics, 70% ethanol alone or products containing at least 70% ethanol were ineffective only against coxsackievirus B3. These results emphasize the care needed in selecting chemical disinfectants for routine use in infection control.

negative: CT Manifestations of Novel Coronavirus Pneumonia: A Case Report BACKGROUND: Since December 2019, the outbreak of the novel coronavirus has impacted nearly >90,000 people in more than 75 countries. In this case report, we aim to define the chest computed tomography findings of 2019-novel coronavirus associated with pneumonia and its successful resolution after treatment. CASE REPORT: A fifty-year-old female patient, who is a businesswoman, presented with chief complaints of “fever for one week, diarrhea, anorexia, and asthenia.” Initially, she was given Tamiflu. The influenza A virus serology was negative. Three days later, levofloxacin was started because the patient’s symptoms did not improve. The novel coronavirus nucleic acid test was negative. It was noted that before the onset of the disease, the patient went to Wuhan on a business trip. Despite the given treatment, her body temperature rose to 39.2°C and she was referred to our clinic for further evaluation. Then, chest computed tomography was performed and showed bilateral multifocal ground glass opacities with consolidation which suggested viral pneumonia as a differential diagnosis, and the subsequent 2019-novel coronavirus pneumonia nucleic acid test was positive. CONCLUSION: Chest computed tomography offers fast and convenient evaluation of patients with suspected 2019-novel coronavirus pneumonia.

negative: Minds, brains, and hearts: an empirical study on pluralism concerning death determination Several authors in bioethics literature have expressed the view that a whole brain conception of death is philosophically indefensible. If they are right, what are the alternatives? Some authors have suggested that we should go back to the old cardiopulmonary criterion of death and abandon the so-called Dead Donor Rule. Others argue for a pluralist solution. For example, Robert Veatch has defended a view that competent persons should be free to decide which criterion of death should be used to determine their death. However, there is very little data on people’s preferences about death determination criteria. We conducted online vignette-based survey with Latvian participants (N = 1416). The data suggest that the pluralist solution fits best with the way our study participants think about death determination—widely differing preferences concerning death determination criteria were observed. Namely, most participants choose one of the three criteria discussed in the literature: whole brain, higher brain, and cardiopulmonary. Interestingly, our data also indicate that study participants tend to prefer less restrictive criteria for determination of their own deaths than for determination of deaths of their closest relatives. Finally, the preferences observed in our sample are largely in accord with the Dead Donor Rule for organ procurement for transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40592-020-00114-0) contains supplementary material, which is available to authorized users.

negative: Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial INTRODUCTION: Chou-Ling-Dan (CLD) (Laggerapterodonta) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza. METHODS AND ANALYSIS: The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems. ETHICS AND DISSEMINATION: The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02662426; Pre-results.

negative: Up to 2.2 million people experiencing disability suffer collateral damage each day of Covid-19 lockdown in Europe. BACKGROUND The Covid-19 pandemic is having a great impact on health services. Patients not receiving care due to closure of outpatient services suffer a collateral damage. Our aim was to provide first data on impact of Covid-19 on people experiencing disability in Europe. METHODS We developed an estimation from a survey and publicly available data. Thirty-eight countries have been inquired through the European Bodies of Physical and Rehabilitation Medicine - the rehabilitation medical specialty. The 9-questions focused on March 31st, 2020. We used the following indicators: for inpatients, acute and rehabilitative hospital beds; for outpatients, missing uniform European data, we used information from Italy, Belgium and UK, and estimated for Europe basing on population, number of rehabilitation physicians, physiotherapists, and people with self-reported limitations. FINDINGS Thirty-five countries (92%) including 99% of the population (809.9 million) answered. Stop of admissions to rehabilitation, early discharge and reduction of activities involved 194,800 inpatients in 10 countries. Outpatient activities stopped for 87%, involving 318,000 patients per day in Italy, Belgium and UK, leading to an estimate range of 1,3-2,2 million in Europe. Seven countries reported experiences on rehabilitation for acute Covid-19 patients. INTERPRETATION Covid-19 emergency is having a huge impact on rehabilitation of people experiencing disability. This may lead to future cumulative effects due to reduced functional outcome and consequent increased burden of care. When the emergency will fade, rehabilitation demand will probably grow due to an expected return wave of these not well treated patients, but probably also of post-Covid-19 patients' needs.

negative: Systematic review and meta-analysis of predictive symptoms and comorbidities for severe COVID-19 infection Background/introduction COVID−19, a novel coronavirus outbreak starting in China, is now a rapidly developing public health emergency of international concern. The clinical spectrum of COVID−19 disease is varied, and identifying factors associated with severe disease has been described as an urgent research priority. It has been noted that elderly patients with pre-existing comorbidities are more vulnerable to more severe disease. However, the specific symptoms and comorbidities that most strongly predict disease severity are unclear. We performed a systematic review and meta-analysis to identify the symptoms and comorbidities predictive of COVID−19 severity. Method This study was prospectively registered on PROSPERO. A literature search was performed in three databases (MEDLINE, EMBASE and Global Health) for studies indexed up to 5th March 2020. Two reviewers independently screened the literature and both also completed data extraction. Quality appraisal of studies was performed using the STROBE checklist. Random effects meta-analysis was performed for selected symptoms and comorbidities to identify those most associated with severe COVID−19 infection or ICU admission. Results Of the 2259 studies identified, 42 were selected after title and abstract analysis, and 7 studies (including 1813 COVID−19 patients) were chosen for inclusion. The ICU group were older (62.4 years) compared to the non-ICU group (46 years), with a significantly higher proportion of males (67.2% vs. 57.1%, p=0.04). Dyspnoea was the only significant symptom predictive for both severe disease (pOR 3.70, 95% CI 1.83 − 7.46) and ICU admission (pOR 6.55, 95% CI 4.28 − 10.0). Notwithstanding the low prevalence of COPD in severe disease and ICU-admitted groups (4.5% and 9.7%, respectively), COPD was the most strongly predictive comorbidity for both severe disease (pOR 6.42, 95% CI 2.44 − 16.9) and ICU admission (pOR 17.8, 95% CI 6.56 − 48.2). Cardiovascular disease and hypertension were also strongly predictive for both severe disease and ICU admission. Those with CVD and hypertension were 4.4 (95% CI 2.64 − 7.47) and 3.7 (95% CI 2.22 − 5.99) times more likely to have an ICU admission respectively, compared to patients without the comorbidity. Conclusions Dyspnoea was the only symptom strongly predictive for both severe disease and ICU admission, and could be useful in guiding clinical management decisions early in the course of illness. When looking at ICU-admitted patients, who represent the more severe end of the spectrum of clinical severity, COPD patients are particularly vulnerable, and those with cardiovascular disease and hypertension are also at a high-risk of severe illness. To aid clinical assessment, risk stratification, efficient resource allocation, and targeted public health interventions, future research must aim to further define those at high-risk of severe illness with COVID−19.

negative: Refugee and migrant health in the COVID-19 response

negative: Age-dependence of mortality from novel coronavirus disease (COVID-19) in highly exposed populations: New York transit workers and residents and Diamond Princess passengers. Background. Populations heavily exposed to the novel coronavirus provide an opportunity to estimate the mortality from COVID-19 in different age groups. Methods. The mortality reported by May 13 from COVID-19 among Diamond Princess cruise ship passengers, and New York residents and Metropolitan Transit Authority (MTA) workers was estimated based on publicly available information. Results. The mortality among children (age 0 to 17 yrs) in New York City was 1 in 172,692. The mortality in New York state was 1 in 322,217 for ages 10-19 yrs., and 1 in 36,725 for ages 20-29 yrs. The mortality among New York transit workers was estimated to be 1 in 7,329 for ages 30-39 years; 1 in 1,075 for ages 40-49 yrs.; 1 in 343 for ages 50-59 yrs.; and 1 in 178 for ages 60-69 yrs. Among Diamond Princess passengers, the mortality was estimated to be 1 in 145 for ages 70-79, and 1 in 54 for ages 80-89. Conclusions: Mortality among populations exposed to the novel coronavirus increases with age, ranging from about 1 in 170,000 below the age of 18 years, to 1 in 54 above the age of 80 years.

negative: Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature Objectives: Coronavirus disease-19 (COVID-19) has spread rapidly around the world, and many risk factors including patient demographics, social determinants of health, environmental variables, underlying health conditions, and adherence to social distancing have been hypothesized to affect case and death rates. However, little has been done to account for the potential confounding effects of these factors. Using a large multivariate analysis, this study illuminates modulators of COVID-19 incidence and mortality in U.S. counties while controlling for risk factors across multiple domains. Methods: Data on COVID-19 and various risk factors in all U.S. counties was collected from publicly available data sources through April 14, 2020. Counties with at least 50 COVID-19 cases were included in case analyses and those with at least 10 deaths were included in mortality models. The 661 counties meeting inclusion criteria for number of cases were grouped into quartiles and comparisons of risk factors were made using t-tests between the highest and lowest quartiles. Similar comparisons for 217 counties were made for above average and below average deaths/100,000. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of factors that significantly impacted cases and deaths. Results: Univariate analyses demonstrated numerous significant differences between cohorts for both cases and deaths. Risk factors associated with increased cases and/or deaths per 100,000 included increased GDP per capita, decreased social distancing, increased age, increased percent Black, decreased percent Hispanic, decreased percent Asian, decreased health, increased poverty, increased diabetes, increased coronary heart disease, increased physical inactivity, increased alcohol consumption, increased tobacco use, and decreased access to primary care. Multivariate regression analyses demonstrated Black race is a risk factor for worse COVID-19 outcome independent of comorbidities, poverty, access to health care, and other mitigating factors. Lower daily temperatures was also an independent risk factor in case load but not deaths. Conclusions: U.S. counties with a higher proportion of Black residents are associated with increased COVID-19 cases and deaths. However, the various suggested mechanisms, such as socioeconomic and healthcare predispositions, did not appear to drive the effect of race in our model. Counties with higher average daily temperatures are also associated with decreased COVID-19 cases but not deaths. Several theories are posited to explain these findings, including prevalence of vitamin D deficiency. Additional studies are needed to further understand these effects.

negative: The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.

negative: Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum

negative: Bevölkerungsbezogene psychische Gesundheit als Schlüsselfaktor im Umgang mit COVID-19 Aim The aim of the article is to point out the important role of prevention and reduction of mental stress in the general population and in sensitive groups in the context of the coronavirus disease 2019 (COVID-19) pandemic. Methods This article includes the analysis and evaluation of studies and recommendations from organizations such as the World Health Organization (WHO) that have examined the psychological consequences of epidemics/pandemics on people and their impact on the further course. Results Fear-related behaviors can adversely affect the course of epidemics. Past outbreaks of infectious diseases (Ebola and Zika virus) have shown that maladaptive behavior, related to increased psychological stress and anxiety, can interfere with the implementation of treatment strategies and actions and can contribute to a further spread. Hereby, strategies for dealing with infectious diseases, that include the suppression of fear, can trigger a vicious circle in which fear and suppression mutually reinforce each other. Conclusion The COVID-19 pandemic poses an immense challenge to governments, health systems and people, with an uncertain outcome, which is associated with a significant burden of mental health in the population. In line with WHO recommendations, national guidelines and preventive measures should include the psychological consequences, the acceptance and normalization of fears and the promotion of resilience in the population in dealing with COVID-19 in order to counteract a further spread.

negative: Bovine herpes virus type 1 induces apoptosis through Fas-dependent and mitochondria-controlled manner in Madin-Darby bovine kidney cells BACKGROUND: Bovine herpesvirus type 1 (BHV-1) is an important pathogen in cattle that is responsible for substantial economic losses. Previous studies suggest that BHV-1 may induce apoptosis in Madin-Darby bovine kidney (MDBK) cells via a mechanism only involving caspases and p53. However, the mechanism for BHV-1-induced MDBK cell apoptosis still requires more research. METHODS: MDBK was used as a model to study the precise signaling pathways of apoptosis induced by BHV-1 infection. RESULTS: BHV-1 infection activated a Fas/FasL-mediated apoptotic pathway, resulting in activation of caspase-8 and cleavage of Bid. In addition, BHV-1 infection down-regulated Bcl-2 and up-regulated Bax expression, thereby initiating the release of cytochrome c followed by caspase-9 activation. The combined activation of the extrinsic and intrinsic pathways resulted in activation of downstream effecter caspase-3 and poly ADP-ribose polymerase (PARP), leading to apoptosis. Furthermore, blocking apoptosis using caspase inhibitors improved BHV-1-infected MDBK cell viability to different extent. BHV-1 infection did not induce significant DNA fragmentation in MDBK cells pretreated with ammonium chloride (NH(4)Cl) or cells infected with UV-inactivated BHV-1. Blocking caspases activation increased BHV-1 replication. CONCLUSIONS: BHV-1 induces apoptosis in MDBK cells through extrinsic and intrinsic pathways and there might be cross-talk between the two pathways. In addition, BHV-1 replication may be necessary for the induction of apoptosis in BHV-1-infected cells, and prolonged cell viability benefits BHV-1 replication.

negative: Can mathematical modelling solve the current Covid-19 crisis? Since COVID-19 transmission started in late January, mathematical modelling has been at the forefront of shaping the decisions around different non-pharmaceutical interventions to confine its’ spread in the UK and worldwide. This Editorial discusses the importance of modelling in understanding Covid-19 spread, highlights different modelling approaches and suggests that while modelling is important, no one model can give all the answers.

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: Why is it difficult to accurately predict the COVID-19 epidemic? Since the COVID-19 outbreak in Wuhan City in December of 2019, numerous model predictions on the COVID-19 epidemics in Wuhan and other parts of China have been reported. These model predictions have shown a wide range of variations. In our study, we demonstrate that nonidentifiability in model calibrations using the confirmed-case data is the main reason for such wide variations. Using the Akaike Information Criterion (AIC) for model selection, we show that an SIR model performs much better than an SEIR model in representing the information contained in the confirmed-case data. This indicates that predictions using more complex models may not be more reliable compared to using a simpler model. We present our model predictions for the COVID-19 epidemic in Wuhan after the lockdown and quarantine of the city on January 23, 2020. We also report our results of modeling the impacts of the strict quarantine measures undertaken in the city after February 7 on the time course of the epidemic, and modeling the potential of a second outbreak after the return-to-work in the city.

negative: The effects of a celebrity suicide on suicide rates in Hong Kong Abstract Background Deaths of celebrities, especially by suicide, can be followed by an increase in population suicide rates, particularly where there is extensive media reporting. We have examined the impact on suicides following the death of a famous Hong Kong pop singer whose death from suicide by jumping from a height, occurred on 1st April 2003, and resulted in extensive and often dramatic media coverage. Methods Data on suicides were obtained from the Hong Kong Census and Statistics Department and the Coroner's Court. The numbers of suicides in 2003 before and after the death of celebrity were compared to the same period in 1998–2002. The case files and suicide notes of people who died by suicide in 2003 were also studied qualitatively. Results There was a significant increase in suicides following the celebrity death, compared with the average over the preceding three months as well as the corresponding monthly average during 1998–2002. It was particularly marked in a subgroup comprising males, aged 25–39 years, many of whom died by jumping. The name of the celebrity was often mentioned in case files and suicide notes. Limitations The statistical results in showing the excess of suicides were based on aggregated data only. Conclusions This study provides further confirmation of the potential harmful consequences of sensational and excessive reporting of celebrity deaths.

negative: Responding to natural disasters vs. disease outbreaks: Do emergency medical service providers have different views? Abstract Introduction Our planet has been experiencing a huge burden of natural disasters and public health emergencies in the last three decades. Emergency medical service providers are expected to be in the frontlines during such emergencies. Yet, this system is badly understudied when it comes to its roles and performance during disasters and public health emergencies. This study is designed to enhance understanding by assessing a sample U.S EMS providers’ views about working during natural disasters and disease outbreaks and explores whether they are coming to work during such conditions. Methods This study utilized a qualitative approach using face-to-face interviews with EMS workers from the State of Delaware, USA. Participants were asked about their views, insights, and potential behavior of working during natural disasters and disease outbreaks. Data collected were transcribed and coded using ATLAS.ti software to develop themes of the study using an inductive approach. Results Three themes were emerged from interviews regarding working during natural disasters; respondents expressed excitement, concern, or no real differences. For disease outbreaks, however, the two themes were concerned and no additional risk. While participants expressed varying concerns about working during disasters and pandemic conditions, everyone felt willing and obligated to come to work despite the perceived high risk for some of them to work in some conditions. Conclusion This study helps to provide the base upon which EMS, public health, and emergency management agencies can formulate actions that emerged from the views of EMS providers concerning work during disasters and public health emergencies.

negative: The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma. The solvent/detergent (SD) process used for plasma can safely inactivate all lipid-enveloped viruses. The introduction of a specific prion-binding ligand gel in combination with SD treatment, time-reduced from 4 to 1-1.5 h, still ensures efficient virus kill, reduces abnormal prion protein by >5 log steps, and preserves levels of plasmin inhibitor at close to the reference range. Infections with known non-enveloped viruses such as HAV or parvovirus B19 are prevented by ensuring low virus loads in the starting plasma units, dilution through pooling of single plasma units, and neutralization of immune antibodies already present in the initial plasma pools. The major advantages of SD plasma over fresh frozen plasma and the other pathogen-inactivated plasmas are its extreme safety with respect to transfusion-related acute lung injury and the significantly lower likelihood of provoking allergic reactions. Both advantages are best interpreted as results of the dilution effect of pooling. No fewer than 18 clinical studies covering all indications for plasma, and extensive clinical experience have shown that reduced levels of coagulation factors and inhibitors as a result of SD treatment do not impair significantly the clinical efficacy or tolerance of plasma. Properly standardized clotting factor and inhibitor potencies and low batch-to-batch variations when compared with single-donor plasma units makes SD plasma more suitable for standardized treatment.

negative: Trend Analysis and Forecasting of COVID-19 outbreak in India COVID-19 is spreading really fast around the world. The current study describes the situation of the outbreak of this disease in India and predicts the number of cases expected to rise in India. The study also discusses the regional analysis of Indian states and presents the preparedness level of India in combating this outbreak. The study uses exploratory data analysis to report the current situation and uses time-series forecasting methods to predict the future trends. The data has been considered from the repository of John Hopkins University and covers up the time period from 30th January 2020 when the first case occurred in India till the end of 24th March 2020 when the Prime Minister of India declared a complete lockdown in the country for 21 days starting 25th March 2020. The major findings show that number of infected cases in India is rising quickly with the average infected cases per day rising from 10 to 73 from the first case to the 300th case. The current mortality rate for India stands around 1.9. Kerala and Maharashtra are the top two infected states in India with more than 100 infected cases reported in each state, respectively. A total of 25 states have reported at least one infected case, however only 8 of them have reported deaths due to COVID-19. The ARIMA model prediction shows that the infected cases in India may reach up to 700 thousands in next 30 days in worst case scenario while most optimistic scenario may restrict the numbers up to 1000-1200. Also, the average forecast by ARIMA model in next 30 days is around 7000 patients from the current numbers of 536. Based on the forecasting model by Holts linear trends, an expected 3 million people may get infected if control measures are not taken in the near future. This study will be useful for the key stakeholders like Government Officials and Medical Practitioners in assessing the trends for India and preparing a combat plan with stringent measures. Also, this study will be helpful for data scientists, statisticians, mathematicians and analytics professionals in predicting outbreak numbers with better accuracy.

negative: Time to ‘Buddy Up’ – Simple Strategies to Support Oncologists During the Covid-19 Pandemic

negative: Should the Holy Week 2020 be cancelled in Latin America due to the COVID-19 pandemic?

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: Excess deaths hidden 100 days after the quarantine in Peru by COVID-19 Objective: To make an estimate of the excess deaths caused by COVID-19 in the non-violent mortality of Peru, controlling for the effect of quarantine. Methods: Analysis of longitudinal data from the departments of Peru using official public information from the National Death Information System and the Ministry of Health of Peru. The analysis is performed between January 1, 2018 and June 23, 2020 (100 days of quarantine). The daily death rate per million inhabitants has been used. The days in which the departments were quarantined with a limit number of accumulated cases of COVID-19 were used to estimate the quarantine impact. Three limits were established for cases: less than 1, 10 and 100 cases. Result: In Peru, the daily death rate per million inhabitants decreased by -1.89 (95% CI: -2.70; -1.07) on quarantine days and without COVID-19 cases. When comparing this result with the total number of non-violent deaths, the excess deaths during the first 100 days of quarantine is 36,230. This estimate is 1.12 times the estimate with data from 2019 and 4.2 times the deaths officers by COVID-19. Conclusion: Quarantine reduced nonviolent deaths; however, they are overshadowed by the increase as a direct or indirect cause of the pandemic. Therefore, the difference between the number of current deaths and that of past years underestimates the real excess of deaths.

negative: Evaluating COVID-19 Public Health Messaging in Italy: Self-Reported Compliance and Growing Mental Health Concerns Purpose: The COVID-19 death-rate in Italy continues to climb, surpassing that in every other country. We implement one of the first nationally representative surveys about this unprecedented public health crisis and use it to evaluate the Italian government's public health efforts and citizen responses. Findings: (1) Public health messaging is being heard. At this point, the Italian people understand how to keep themselves and others safe from the SARS-Cov-2 virus. This is true for all population groups we studied, with the partial exception of slightly lower compliance among young adults. Remarkably, even those who do not trust the government, and those who think the government has been untruthful about the crisis mostly believe the public health message and claim to be acting in accordance. (2) The quarantine is beginning to have serious negative effects on the population's mental health. Policy Recommendations: Public health messaging is being heard and understood. The focus now should move from explaining that citizens should stay at home to what they can do at home. We need interventions that make staying at home and following public health protocols more desirable, or possibly even fun. These interventions could include virtual social interactions, such as online social reading activities, classes, exercise routines, among others - all designed to reduce the boredom of being socially isolated for long periods of time and to increase the attractiveness of following public health recommendations. Interventions like these will grow in importance as the crisis wears on around the world, and staying inside wears on people.

negative: COVID-19 detection using deep learning models to exploit Social Mimic Optimization and structured chest X-ray images using fuzzy color and stacking approaches Abstract Coronavirus causes a wide variety of respiratory infections and it is an RNA-type virus that can infect both humans and animal species. It often causes pneumonia in humans. Artificial intelligence models have been helpful for successful analyses in the biomedical field. In this study, Coronavirus was detected using a deep learning model, which is a sub-branch of artificial intelligence. Our dataset consists of three classes namely: coronavirus, pneumonia, and normal X-ray imagery. In this study, the data classes were restructured using the Fuzzy Color technique as a preprocessing step and the images that were structured with the original images were stacked. In the next step, the stacked dataset was trained with deep learning models (MobileNetV2, SqueezeNet) and the feature sets obtained by the models were processed using the Social Mimic optimization method. Thereafter, efficient features were combined and classified using Support Vector Machines (SVM). The overall classification rate obtained with the proposed approach was 99.27%. With the proposed approach in this study, it is evident that the model can efficiently contribute to the detection of COVID-19 disease.

negative: Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease Abstract The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside Wuhan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).

negative: Medical imaging informatics research and development trends—an editorial

negative: A review on the antagonist Ebola: A prophylactic approach Abstract Ebola virus (EBOV), a member of Filoviridae virus family under the genus Ebolavirus, has emerged as a dangerous and potential threat to human health globally. It causes a severe and deadly hemorrhagic fever in humans and other mammals, called Ebola Virus Disease (EVD). In recent outbreaks of EVD, there has been loss of large numbers of individual’s life. Therefore, EBOV has attracted researchers and increased interests in developing new models for virus evolution, and therapies. The EBOV interacts with the immune system of the host which led to understand how the virus functions and effects immune system behaviour. This article presents an exhaustive review on Ebola research which includes EVD illness, symptoms, transmission patterns, patho-physiology conditions, development of antiviral agents and vaccines, resilient health system, dynamics and mathematical model of EBOV, challenges and prospects for future studies.

negative: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.

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: 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: The use of simulation to prepare for changes in emergent airway management in the early days of the Covid-19 outbreak

negative: Molecular immune pathogenesis and diagnosis of COVID-19 Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.

negative: Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? Amid of coronavirus disease 2019 (Covid-19) pandemic, much emphasis was initially placed on the elderly or those who have preexisting health conditions such as obesity, hypertension, and diabetes as being at high risk of contracting and/or dying of Covid-19. But it is now becoming clear that being male is also a factor. The epidemiological findings reported across different parts of the world indicated higher morbidity and mortality in males than females. While it is still too early to determine why the gender gap is emerging, this article point to several possible factors such as higher expression of angiotensin-converting enzyme-2 (ACE 2; receptors for coronavirus) in male than female, sex-based immunological differences driven by sex hormone and X chromosome. Furthermore, a large part of this difference in number of deaths is caused by gender behavior (lifestyle), i.e., higher levels of smoking and drinking among men compared to women. Lastly, studies reported that women had more responsible attitude toward the Covid-19 pandemic than men. Irresponsible attitude among men reversibly affect their undertaking of preventive measures such as frequent handwashing, wearing of face mask, and stay at home orders.

negative: Prediction of Coronavirus Disease (covid-19) Evolution in USA with the Model Based on the Eyring Rate Process Theory and Free Volume Concept A modification arguing that the human movement energy may change with time is made on our previous infectious disease model, in which infectious disease transmission is considered as a sequential chemical reaction and reaction rate constants obey the Eyrings rate process theory and free volume concept. The modified model is employed to fit current covid-19 outbreak data in USA and to make predictions on the numbers of the infected, the removed and the death in the foreseeable future. Excellent fitting curves and regression quality are obtained, indicating that the model is working and the predictions may be close to reality. Our work could provide some ideas on what we may expect in the future and how we can prepare accordingly for this difficult period.

negative: Social interventions can lower COVID-19 deaths in middle-income countries A novel pandemic coronavirus disease (COVID-19) was first detected in late 2019 in Wuhan (China)1,2. COVID-19 has caused 77 national governments worldwide to impose a lockdown in part or all their countries, as of April 4, 20203. The United States and the United Kingdom estimated the effectiveness of non-pharmaceutical interventions to reduce COVID-19 deaths, but there is less evidence to support choice of control measures in middle-income countries4. We used Colombia, an upper-middle income country, as a case-study to assess the effect of social interventions to suppress or mitigate the COVID-19 pandemic. Here we show that a combination of social distancing interventions, triggered by critical care admissions, can suppress and mitigate the peak of COVID-19, resulting in less critical care use, hospitalizations, and deaths. We found, through a mathematical simulation model, that a one-time social intervention may delay the number of critical care admissions and deaths related to the COVID-19 pandemic. However, a series of social interventions (social and work distance and school closures) over a period of a year can reduce the expected burden of COVID-19, however, these interventions imply long periods of lockdown. Colombia would prevent up to 97% of COVID-19 deaths using these triggered series of interventions during the first year. Our analyses could be used by decision-makers from other middle-income countries with similar demographics and contact patterns to Colombia to reduce COVID-19 critical care admissions and deaths in their jurisdictions.

negative: HATRIC: a study of Pelargonium sidoides root extract EPs®7630 (Kaloba®) for the treatment of acute cough due to lower respiratory tract infection in adults—study protocol for a double blind, placebo-controlled randomised feasibility trial BACKGROUND: Acute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial. We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included. METHODS: The HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care. Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place. DISCUSSION: If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care. TRIAL REGISTRATION: HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.

negative: Dental journals and coronavirus disease (COVID-19): A current view

negative: 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.

negative: Coronavirus Disease‐2019 with Dermatologic Manifestations and Implications: An Unfolding Conundrum The novel coronavirus SARS‐CoV‐2 has caused Coronavirus Disease‐2019, widely known as COVID‐19, now a pandemic with extraordinary infectivity, mortality, and fomite adhesiveness. As a nosocomial infection for hospital and nursing home patients and health care workers, it represents an extraordinary challenge. The cutaneous markers of this pandemic are being elucidated with preliminary experiences being shared and rapidly communicated. We will review COVID‐19 from both a dermatologic and public health perspective. This article is protected by copyright. All rights reserved.

negative: Relative disease burdens of COVID-19 and seasonal influenza in New York City, February 1 - April 18, 2020. Comparisons between the mortality burdens of COVID-19 and seasonal influenza often fail to account for the fact that the United States Centers for Disease Control and Prevention (CDC) reports annual influenza mortality estimates which are calculated based upon a series of assumptions about the underreporting of flu deaths. COVID-19 deaths, in contrast, are being reported as raw counts. In this report, we compare COVID-19 death counts to seasonal influenza death counts in New York City during the interval from February 1 - April 18, 2020. Using this approach, COVID-19 appears to have caused 21.4 times the number of deaths as seasonal influenza during the same period. We also assessed excess mortality in order to verify this finding. New York City has had approximately 13,032 excess all-cause mortality deaths during this time period. We assume that most of these deaths are COVID-19 related. We therefore calculated the ratio of excess deaths (i.e. assumed COVID-19 deaths) to seasonal influenza deaths during the same time interval and found a similar ratio of 21.1 COVID-19 to seasonal influenza deaths. Our findings are consistent with conditions on the ground today. Comparing COVID-19 deaths with CDC estimates of yearly influenza-related deaths would suggest that, this year, seasonal influenza has killed approximately the same number of Americans as COVID-19 has. This does not comport with the realities of the pandemic we see today.

negative: Assessment of the impact of media coverage in coronavirus-related Google Trends: Infodemiology study. BACKGROUND The influence of media coverage in online searches may hamper the role of Google Trends (GT) for Covid-19 monitoring. OBJECTIVE To assess whether Covid-19-related GT - particularly on ageusia and anosmia - were primarily related to media coverage or with epidemic trends. METHODS We retrieved GT data for searches on "coronavirus", "cough", "anosmia" and "ageusia", plotting them for a period of 5 years. In addition, we analysed the trends of those queries for 17 countries throughout the year of 2020, particularly concerning rises and peaks of searches. For anosmia and ageusia, we assessed whether the respective GT correlated with Covid-19 cases and deaths both throughout 2020 and specifically before March 16, 2020 (i.e., the date when the media started reporting that those symptoms could be associated with Covid-19). RESULTS Over the last five years, peaks of "coronavirus" GT were only observed during the Winter of 2020. Rises and peaks in "coronavirus" searches were similar in time in the 17 different assessed countries, irrespectively of their epidemic situation. In 15 of these countries, rises in "anosmia" and "ageusia" GT occurred in the same week or one week after they were identified in the media as symptoms of Covid-19. Analysing data prior to March 16, 2020, anosmia/ageusia GT were found to have variable correlation with Covid-19 cases and deaths in the different countries. CONCLUSIONS Covid-19-related GT is more related to media coverage than with epidemic trends. CLINICALTRIAL

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: China’s Internationalized Higher Education During Covid-19: Collective Student Autoethnography This article presents 15 autoethnographical texts detailing student experiences at Beijing Normal University in the midst of the Covid-19 pandemic. Contributions have been collected over 6 weeks between 15 February and 1 April 2020, edited by Hejia Wang (assisted by Moses Oladele Ogunniran and Yingying Huang), and supervised by Michael Peters. Through shared in-depth empirical feelings and representations from a wide variety of cultural, historical, and social contexts, the article outlines an answer to the question: How do students, connected virtually but separated physically in an internationalized university, deal with disruption brought about by the Covid-19 pandemic? Student testimonies offer reflections on Covid-19 and Chinese international education, experiences of online teaching and learning, reflections on university coping mechanisms, an account of realities and feelings related to changes in academic life, and discussions on coping strategies in Chinese international higher education. Contributors expose their individual feelings, effects, benefits, challenges, and risk management strategies. Collected at the peak of the Covid-19 pandemic, these testimonies are unable to offer systemic answers to challenges facing the whole world. However, these experiences and feelings will provide important inputs to global discussions about the future of the world, after Covid-19.

negative: Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data Background The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Results From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%～19.5% and the instant cured rate was 80.0%～96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%～16.6% and the instant cured rate was 83.4%～96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively. Conclusions The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.

negative: Diseases affecting patients returning from abroad: Experience of a travel clinic in Japan from 2004 to 2014 Abstract The number of patients returning from or staying abroad is likely to increase in the future. We performed a retrospective study of patients returning from abroad in our travel clinic in Japan. All patients presenting within 6 months of traveling abroad between 2004 and 2014 were included in the present study. A total of 2374 (mean age, 35 years) patients were seen by doctors specializing in treating infectious diseases. Of these, 918 were females and 87 of them lived abroad. Diagnoses and exposure regions were recorded for all patients. The most frequent region visited before attending our clinic was Southeast Asia (n = 1050, 44%), with a median duration for staying abroad of 8 days. The major purposes for overseas travel were tourism (n = 1302, 55%) and business (n = 684, 29%). Of the 2399 individual diagnoses made, the most frequent were diseases of the gastrointestinal system (n = 1083, 45%), skin and soft tissue (n = 440, 18%), systemic febrile disease without specific systems (419, 18%), and the respiratory system (353, 15%). The relative incidences of specific diseases changed drastically due to significant disease outbreaks, such as pandemic influenza in 2009. Exposure regions remained relatively constant throughout the study period, except for Japan. Vaccine-preventable diseases accounted for 5.3% of all the diseases, and 402 (26%) patients received pre-travel consultation and prophylaxis with vaccines and/or anti-malarial drug. We should make an effort to make more people notice the risk of travel and properly perform prophylaxis.

negative: Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

negative: TADs in the Dromedary The transboundary diseases in camel are mainly linked to the regional camel meat market from Sahelian countries (from Mauritania to Somalia) to the Arabian peninsula and North Africa. Indeed, the camel flow in relationship with this market is based on live animals’ export. Because the camel trade can be formal and informal with interconnections between both sectors and despite veterinary controls in the main exporting ports, some diseases such as Rift Valley fever (RVF), PPR-like disease, and MERS-coronavirus can spread from exporting countries to importing ones. However, the epidemiological status of these different diseases is quite variable and the transmission to humans in case of zoonosis (RVF and MERS-Cov) is not necessarily due to transboundary camel trade despite the impact of outbreak on the regional camel market. Globally, dromedary camel is less affected than other ruminants by infectious diseases under transboundary surveillance. But, because camel breeding is concentrated in countries where the disease surveillance systems often lack means, where the frontiers in desert areas are often “porous,” and where the herd mobility is difficult to assess, the risk of transboundary diseases’ transmission through borders is not negligible. Nowadays, the challenge of TADs control is limited to Rift Valley fever, but special attention must be paid to emerging diseases, including the recent discovery of prion disease in Algeria.

negative: When health professionals look death in the eye: the mental health of professionals who deal daily with the 2019 coronavirus outbreak BACKGROUND: The fact that COVID-19 is transmissible from human to human and associated with high morbidity and potentially fatality can intensify the perception of personal danger. In addition, the foreseeable shortage of supplies and an increasing flow of suspected and real cases of COVID-19 contribute to the pressures and concerns of health professionals. METHOD: The studies were identified in well-known international journals found in two electronic databases: Scopus and Embase. The data were cross-checked with information from the main international newspapers. RESULTS: Work-related stress is a potential cause of concern for health professionals. It has been associated with anxiety including multiple clinical activities, depression in the face of the coexistence of countless deaths, long work shifts with the most diverse unknowns and demands in the treatment with patients with COVID-19. Therefore, it is an important indicator of psychic exhaustion. CONCLUSIONS: As coronavirus cases increase and deaths surge in Italy, new figures show an "enormous" level of contagion among the country's medical personnel. At least 2,629 health workers have been infected with coronavirus since the outbreak onset in February, representing 8.3% of total cases. The percentage of infected health workers has almost doubled the number registered in China throughout the epidemic. Intensive care unit physicians are on their stress limit, especially when dealing with older patients and with death prospects. Doctors, not a relative, are inevitably the last people a dying COVID-19 patient will see.

negative: Non-Adherence Tree Analysis (NATA) - an adherence improvement framework: a COVID-19 case study Poor adherence to medication is a global phenomenon that has received a significant amount of research attention yet remains largely unsolved. Medication non-adherence can blur drug efficacy results in clinical trials, lead to substantial financial losses, increase the risk of relapse and hospitalisation, or lead to death. The most common methods measuring adherence are post-treatment measures; that is, adherence is usually measured after the treatment has begun. What the authors are proposing in this multidisciplinary study is a technique for analysing the factors that can cause non-adherence before or during medication treatment. Fault Tree Analysis (FTA), allows system analysts to determine how combinations of simple faults of a system can propagate to cause a total system failure. Monte Carlo simulation is a mathematical algorithm that depends heavily on repeated random sampling to predict the behaviour of a system. In this study, the authors propose the use of Non-Adherence Tree Analysis (NATA), based on the FTA and Monte Carlo simulation techniques, to improve adherence. Firstly, the non-adherence factors of a medication treatment lifecycle are translated into what is referred to as a Non-Adherence Tree (NAT). Secondly, the NAT is coded into a format that is translated into the GoldSim software for performing dynamic system modelling and analysis using Monte Carlo. Finally, the GoldSim model is simulated and analysed to predict the behaviour of the NAT. This study produces a framework for improving adherence by analysing social and non-social adherence barriers. The results reveal that the biggest factor that could contribute to non-adherence to a COVID-19 treatment is a therapy-related factor (the side effects of the medication). This is closely followed by a condition-related factor (asymptomatic nature of the disease) then patient-related factors (forgetfulness and other causes). With this information, clinicians can implement relevant measures and allocate resources appropriately to minimise non-adherence.

negative: Suppression of MHV3 virus-activated macrophages by dieldrin Abstract Dieldrin (36 mg/kg body weight) administered intraperitoneally prolonged recovery from infection with mouse hepatitis virus 3 (MHV3) in the genetically-resistant A/J strain, affected the humoral anti-MHV3 IgG immune response, and inhibited the intrinsic antiviral activity of peritoneal macrophages upon in vitro rechallenge with the virus. Infection of untreated A/J animals and vehicle controls with MHV3 resulted in marked and reproducible activation of peritoneal macrophages, observed in vitro as resistance to MHV3-cytopathic effects 48 hr after rechallenge with the virus, whereas exposure to dieldrin resulted in apparent loss of the intrinsic capacity of cells to restrict replication of MHV3 and to protect them from cytolysis. In addition, in vitro treatment of MHV3 virus-activated macrophages with dieldrin, mitomycin C and X-irradiation, inhibited the intrinsic capacity of cells to restrict MHV3 replication. This mechanism of cellular restriction of the virus by MHV3-activated macrophages from the resistant A/J strain appeared to be one of the sensitive targets for the suppressive action of dieldrin on host resistance, as (i) no major changes in macrophage cellular parameters were observed in in vitro studies of cell viability, adherence to plastic, and Superoxide anion generation; (ii) the increased cell yield in the peritoneal exudates during MHV3 virus infection was not affected by dieldrin exposure; and (iii) the attachment and uptake of [3H]MHV3 by virus-activated macophages was shown to be unchanged by dieldrin exposure.

negative: Coronavirus and financial volatility: 40 days of fasting and fear 40 days after the start of the international monitoring of COVID-19, we search for the effect of official announcements regarding new cases of infection and death ratio on the financial markets volatility index (VIX). Whereas the new cases reported in China and outside China have a mixed effect on financial volatility, the death ratio positively influences VIX, that outside China triggering a more important impact. In addition, the higher the number of affected countries, the higher the financial volatility is.

negative: Predict the next moves of COVID-19: reveal the temperate and tropical countries scenario The spread of COVID-19 engulfs almost all the countries and territories of the planet, and infections and fatality are increasing rapidly. The first epi-center of its' massive spread was in Wuhan, Hubei province, China having a temperate weather, but the spread has got an unprecedented momentum in European temperate countries mainly in Italy and Spain (as of March 30, 2020). However, Malaysia and Singapore and the neighboring tropical countries of China got relatively low spread and fatality that created a research interest on whether there are potential impacts of weather condition on COVID-19 spread. Adopting the SIR (Susceptible Infected Removed) deviated model to predict potential cases and death in the coming days from COVID-19 was done using the secondary and official sources of data. This study shows that COVID-19 spread and fatality tend to be high across the world but compared to tropical countries, it is going to be incredibly high in the temperate countries having lower temperature (7-16°C) and humidity (80-90%) in last March. However, some literature predicted that this might not to be true, rather irrespective of weather conditions there might be a continuous spread and death. Moreover, a large number of asymptotic COVID-19 carrier in both temperate and tropical countries may re-outbreak in the coming winter. Therefore, a comprehensive global program with the leadership of WHO for testing of entire population of the world is required, which will be very useful for the individual states to take proper political action, social movement and medical services.

negative: Clinical features and outcomes of 197 adult discharged patients with COVID-19 in Yichang, Hubei Purpose To investigate the epidemiology and clinical features of discharged adult patients with COVID-19 in Yichang. Method The retrospective study recruited 197 cases of COVID-19 discharged from Yichang Central People's Hospital and Yichang Third People's Hospital from Jan 17 to Feb 26, 2020. All cases were confirmed by real-time RT-PCR or chest computer tomography (CT).The survivors were followed up until March 4,2020. Clinical data, including demographic characteristic, presentation, exposure history, laboratory examination, radiology and prognosis were enrolled and analyzed by SPSS 19.0 software. Results There were 197 adult discharged patients with COVID-19 in this study. Statistical analysis indicated that the average age was 55.94 years, and female patients were 50.3%. Those patients mainly resided in urban with exposure history in 2 weeks. Fever, cough and weakness were the common symptoms. Leucocytes were mainly normal or decreased in 185 patents, both lymphocytes and eosinophils reduced, the ratios were 56.9% and 50.3%, respectively. On the contrary, lactate dehydrogenases raised in 65 patients. C-reactive protein elevated in the most of patients. The sensitivity of RT-PCR was 63.5%. Chest CT indicated that bilateral patchy shadows were the most common imaging manifestations.169 patients recovered and transferred to a designated hospital for observation, and the others turned worst and died of acute respiratory failure. Conclusion COIVD-19 infection have become a life-threaten public health problem, the sensitivity of RT-PCR was limited. Chest CT scan was recommended for the suspected patients. Moreover, lymphocytopenia and eosinophils declining without leukocytes increasing may be considered as a useful evidence for the diagnosis.

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: 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: Who dies from COVID-19? Post-hoc explanations of mortality prediction models using coalitional game theory, surrogate trees, and partial dependence plots As of early June, 2020, approximately 7 million COVID-19 cases and 400,000 deaths have been reported. This paper examines four demographic and clinical factors (age, time to hospital, presence of chronic disease, and sex) and utilizes Shapley values from coalitional game theory and machine learning to evaluate their relative importance in predicting COVID-19 mortality. The analyses suggest that out of the 4 factors studied, age is the most important in predicting COVID-19 mortality, followed by time to hospital. Sex and presence of chronic disease were both found to be relatively unimportant, and the two global interpretation techniques differed in ranking them. Additionally, this paper creates partial dependence plots to determine and visualize the marginal effect of each factor on COVID-19 mortality and demonstrates how local interpretation of COVID-19 mortality prediction can be applicable in a clinical setting. Lastly, this paper derives clinically applicable decision rules about mortality probabilities through a parsimonious 3-split surrogate tree, demonstrating that high-accuracy COVID-19 mortality prediction can be achieved with simple, interpretable models.

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: Compassion in the Clinical Context: Constrained, Distributed, and Adaptive BACKGROUND: Compassion is intrinsically situated within particular contexts and how these contexts can shape compassion has not been well-described. OBJECTIVE: The purpose of the study was to describe how individual and contextual challenges can impact compassion within critical care and palliative care settings. DESIGN: This qualitative study adopted phenomenology and autoethnography to inform data collection, and principles of activity theory and realist inquiry for data interpretation. PARTICIPANTS: Five clinicians who work in critical care (n = 3) and palliative care (n = 3) participated in the study. APPROACH: Qualitative data were obtained from ethnographic observations, interviews, and focus groups. Participants observed and recorded field notes (n = 53) on instances of suffering and compassion in their workplace settings. At the end of the study period, they participated in a focus group or individual interview to reflect on their experiences. Data was analyzed using constructivist grounded theory techniques and iteratively synthesized through group discussion and model building. KEY RESULTS: The findings reflected four phenomena associated with compassion in context: individual gaps and lapses in compassion, relational challenges, contextual constraints on compassion, and distributed compassion. Individual gaps and lapses in compassion involved inattention, intention vs. perception, personal capacity, and personal toll. Relational challenges included receptivity, fragmentation, and lack of shared understanding. Contextual constraints consisted of situational pressures, the clinical environment, gaps in education, and organizational culture. The distribution of compassion within teams and how teams adapt their behaviors in response to perceived needs for greater compassion modulated these challenges. CONCLUSIONS: The study illustrates the many ways in which compassion can be shaped by context and highlights the role of teamwork in identifying gaps and lapses in compassion and responding in a way that supports patients, families, and colleagues. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-019-05467-9) contains supplementary material, which is available to authorized users.

negative: Prognostic value of NT-proBNP in patients with severe COVID-19 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 was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of in-hospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19.

negative: Hypothesized behavioral host manipulation by SARS-CoV2 / COVID-19 infection Abstract Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host’s central nervous system and triggers hyper aggression. The virus is also present in the rabid animal’s saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.

negative: From SARS-CoV to SARS-CoV-2: safety and broad-spectrum are important for coronavirus vaccine development The global pandemic of COVID-19 caused by SARS-CoV-2 (also known as 2019-nCoV and HCoV-19) has posed serious threats to public health and economic stability worldwide, thus calling for development of vaccines against SARS-CoV-2 and other emerging and reemerging coronaviruses. Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines. In this review, we summarized the current knowledge on the advantages and disadvantages of the SARS-CoV vaccine candidates and prospected the strategies for the development of safe, effective and broad-spectrum coronavirus vaccines for prevention of infection by currently circulating SARS-CoV-2 and other emerging and reemerging coronaviruses that may cause future epidemics or pandemics.

negative: SARS-CoV-2: The Lombardy scenario in numbers

negative: [Laboratory testing techniques for SARS-CoV-2]. The ongoing epidemic of caused by the coronavirus SARS-CoV-2 starting in December 2019 poses a serious public health threat globally. The virus is highly infectious and transmitted mainly through droplets and contacts, and is associated with a high risk of pneumonia. A small number of patients may present with acute respiratory distress syndrome with severe respiratory complications, which can lead even to death. The selection of appropriate detection techniques and methods for accurate and rapid identification of pathogens therefore plays a key role in improving the diagnosis and treatment of the patients and containing the outbreak. In this review, the authors gives an overview of the virus laboratory detection technology, including virus isolation and culture, real-time fluorescent PCR, gene sequencing, serological antibody detection, and the gene editing technology based on CRISPR/Cas13 system. These techniques are expected to provide valuable assistance in controlling the epidemic and new ideas for future researches.

negative: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Abstract Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.

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: Epidemiological parameter review and comparative dynamics of influenza, respiratory syncytial virus, rhinovirus, human coronavirus, and adenovirus Influenza-like illness (ILI) accounts for a large burden of annual morbidity and mortality worldwide. A finer-grained knowledge of the parameters and dynamics of the viruses commonly underlying ILI is needed for modeling, diagnostic, and intervention efforts. We conducted an extensive literature review for epidemiological parameter values for influenza, respiratory syncytial virus (RSV), rhinovirus, human coronavirus (HCoV), and adenovirus. We also developed a deterministic SEIR model for ILI, and derived an expression for R0. We here report ranges and means for parameters for these five common viruses.

negative: A commentary on “World Health Organization declares global emergency: A review of the 2019 novel Coronavirus (COVID-19)”

negative: The COVID-19 Infection in Italy: A Statistical Study of an Abnormally Severe Disease We statistically investigate the Coronavirus Disease 19 (COVID-19) pandemic, which became particularly invasive in Italy in March 2020. We show that the high apparent lethality or case fatality ratio (CFR) observed in Italy, as compared with other countries, is likely biased by a strong underestimation of the number of infection cases. To give a more realistic estimate of the lethality of COVID-19, we use the actual (March 2020) estimates of the infection fatality ratio (IFR) of the pandemic based on the minimum observed CFR and analyze data obtained from the Diamond Princess cruise ship, a good representation of a “laboratory” case-study from an isolated system in which all the people have been tested. From such analyses, we derive more realistic estimates of the real extent of the infection as well as more accurate indicators of how fast the infection propagates. We then isolate the dominant factors causing the abnormal severity of the disease in Italy. Finally, we use the death count—the only data estimated to be reliable enough—to predict the total number of people infected and the interval of time when the infection in Italy could end.

negative: Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.

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: Remdesivir bei Patienten mit schwerer COVID-19

negative: SARS: Epidemiology, Clinical Presentation, Management, and Infection Control Measures Severe acute respiratory syndrome (SARS) is a recently recognized febrile respiratory illness that first appeared in southern China in November 2002, has since spread to several countries, and has resulted in more than 8000 cases and more than 750 deaths. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus. It appears to be spread primarily by large droplet transmission. There is no specific therapy, and management consists of supportive care. This article summarizes currently available information regarding the epidemiology, clinical features, etiologic agent, and modes of transmission of the disease, as well as infection control measures appropriate to contain SARS.

negative: COVID-19, Modern Pandemic: A Systematic Review From Front-Line Health Care Providers’ Perspective Coronavirus disease 2019 (COVID-19) caused infection in 168,000 cases worldwide in about 148 countries and killed more than 6,610 people around the world as of March 16, 2020, as per the World Health Organization (WHO). Compared to severe acute respiratory syndrome and Middle East respiratory syndrome, there is the rapid transmission, long incubation period, and disease containment is becoming extremely difficult. The main aim of this systematic review is to provide a comprehensive clinical summary of all the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19, thus increasing awareness in health care providers. We also discussed various preventive measures to combat COVID-19 effectively. A systematic and protocol-driven approach is needed to contain this disease, which was declared as a global pandemic on March 11, 2020, by the WHO.

negative: The impact of 2019 novel coronavirus on heart injury: A systemic review and Meta-analysis Abstract Background Evidence about COVID-19 on cardiac injury is inconsistent. Objectives We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. Methods We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase–MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). Results We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase–MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. Conclusion The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.

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: COVID-19 in a tertiary hospital from Romania: Epidemiology, preparedness and clinical challenges

negative: Evaluating the virucidal efficacy of hydrogen peroxide vapour Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces.

negative: Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E. A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.

negative: Infectious disease pandemic planning and response: Incorporating decision analysis Freya Shearer and co-authors discuss the use of decision analysis in planning for infectious disease pandemics.

negative: Extended SIR prediction of the epidemics trend of COVID-19 in Italy and compared with Hunan, China Background: Coronavirus Disease 2019 (COVID19) is currently a global public health threat. Outside of China, Italy is one of the most suffering countries with the COVID19 epidemic. It is important to predict the epidemics trend of COVID19 epidemic in Italy to help develop public health strategies. Methods: We used time series data of COVID 19 from Jan 22,2020 to Mar 16,2020. An infectious disease dynamic extended susceptible infected removed (eSIR) model, which covers the effects of different intervention measures in dissimilar periods, was applied to estimate the epidemic trend in Italy. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credible interval (CI). Hunan, with similar total number of populations in Italy, was used as a comparative item. Results: In the eSIR model, we estimated that the basic reproductive number for COVID 19 was respectively 4.10 (95% CI: 2.15 to 6.77) in Italy and 3.15(95% CI: 1.71 to 5.21) in Hunan. There would be totally 30 086 infected cases (95%CI:7920-81 869) under the current country blockade and the endpoint would be Apr 25 (95%CI: Mar 30 to Aug 07) in Italy. If the country blockade is imposed 5 day later, the total number of infected cases would expand the infection scale 1.50 times. Conclusion: Italy's current strict measures can efficaciously prevent the further spread of COVID19 and should be maintained. Necessary strict public health measures be implemented as soon as possible in other European countries with a high number of COVID19 cases. The most effective strategy needs to be confirmed in further studies.

negative: Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19

negative: Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic During a pandemic, robust estimation of case fatality rates (CFRs) is essential to plan and control suppression and mitigation strategies. At present, estimates for the CFR of COVID-19 caused by SARS-CoV-2 infection vary considerably. Expert consensus of 0.1-1% covers in practical terms a range from normal seasonable Influenza to Spanish Influenza. In the following, I deduce a formula for an adjusted Infection Fatality Rate (IFR) to assess mortality in a period following a positive test adjusted for selection bias. Official datasets on cases and deaths were combined with data sets on number of tests. After data curation and quality control, a total of IFR (n=819) was calculated for 21 countries for periods of up to 26 days between registration of a case and death. Estimates for IRFs increased with length of period, but levelled off at >9days with a median for all 21 countries of 0.11 (95%-CI: 0.073-0.15). An epidemiologically derived IFR of 0.040 % (95%-CI: 0.029%-0.055%) was determined for Iceland and was very close to the calculated IFR of 0.057% (95%-CI: 0.042-0.078), but 2.7-6-fold lower than CFRs. IFRs, but not CFRs, were positively associated with increased proportions of elderly in age-cohorts (n=21, spearman's ρ =.73, p =.02). Real-time data on molecular and serological testing may further displace classical diagnosis of disease and its related death. I will critically discuss, why, how and under which conditions the IFR, provides a more solid early estimate of the global burden of a pandemic than the CFR.

negative: On the corona infection model with contact restriction This article presents a mathematical infection model that is designed to estimate the course of coronavirus infection in Germany for several days in advance: How many people become ill or die, what is the temporal development? If the contact restriction is perfect, then the model predicts the development of the virus infection after the initial subsidence of the infection. However, since this restriction cannot always be strictly adhered to, the model is dynamically adapted to the development. This makes it possible to estimate the number of infected people, the number of new infections and deaths in Germany about a week in advance.

negative: Mutterschutz – auch im Zeitalter der Coronakrise Pregnant employees should be protected, particularly in crisis situations. The Maternity Protection Act states that employees are not allowed to have contact with infectious people, including people with SARS-CoV-2 infections; no new regulation is required here.

negative: Spatial Correlation of Particulate Matter Pollution and Death Rate of COVID-19 The Coronavirus (COVID-19) epidemic, which was first reported in December 2019 in Wuhan, China, has caused 3,314 death as of March 31, 2020 in China. This study aimed to investigate the spatial associations of daily particulate matter (PM) concentrations with death rate of COVID-19 in China. We conducted a cross-sectional analysis to examine the spatial associations of daily PM2.5 and PM10 concentrations with death rate of COVID-19 in China through multiple linear regression method. We found that COVID-19 held higher death rates with increasing concentration of PM2.5 and PM10 levels in the spatial scale, which may affect the process of patients developed from mild to severe and finally influence the prognosis of COVID-19 patients.

negative: When basic supplies are missing, what to do? Specific demands of the local street population in times of coronavirus – a concern of social psychiatry Abstract Background Homeless experts and some federal housing officials are sounding the alarm that the patchwork of government efforts to address the coronavirus outbreak risks leaving out one group of acutely vulnerable people: the homeless. In terms of isolation, it is too unclear what that looks like if you normally sleep on the streets. In this tough moment, when people should be turned away, not only it feels inhumane, but it is also a big public health risk, because where are they going to go? Method The studies were identified using large-sized newspapers with international circulation Results With more cities suspecting community transmission of the novel coronavirus, people who sleep in shelters or hunker down outside already have a lower life expectancy and often have underlying health conditions that put them at greater risk if they develop COVID-19 (Global News, 2020). These people face lack of sleep, malnutrition, and “extreme stress levels just to meet their daily needs”, all of which weakens the immune system. Along with mental illness or substance abuse disorders, they are “incredibly vulnerable to this virus”. Conclusions Health organizations are well aware of the risks involved in mental health. A large population of homeless people experience their pain and psychological distress intermittently. For low-income patients, the various borderline situations related to health/illness involve growing expectations regarding the basic needs. This is a serious concern when linked to the pandemic.

negative: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy Cytokine storms are drivers of pathology and mortality in myriad viral infections affecting the human population. In SARS-CoV-2-infected patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress syndrome, myocardial damage, and death. However, the therapeutic value of attenuating the cytokine storm in COVID-19 remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome (DS) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity, accompanying cytokine storm, and liver hyperinflammation are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic. One Sentence Summary Inhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice.

negative: Death anxiety in the time of COVID-19: theoretical explanations and clinical implications The recent COVID-19 pandemic has triggered a surge in anxiety across the globe. Much of the public’s behavioural and emotional response to the virus can be understood through the framework of terror management theory, which proposes that fear of death drives much of human behaviour. In the context of the current pandemic, death anxiety, a recently proposed transdiagnostic construct, appears especially relevant. Fear of death has recently been shown to predict not only anxiety related to COVID-19, but also to play a causal role in various mental health conditions. Given this, it is argued that treatment programmes in mental health may need to broaden their focus to directly target the dread of death. Notably, cognitive behavioural therapy (CBT) has been shown to produce significant reductions in death anxiety. As such, it is possible that complementing current treatments with specific CBT techniques addressing fears of death may ensure enhanced long-term symptom reduction. Further research is essential in order to examine whether treating death anxiety will indeed improve long-term outcomes, and prevent the emergence of future disorders in vulnerable populations. KEY LEARNING AIMS: (1).. To understand terror management theory and its theoretical explanation of death anxiety in the context of COVID-19. (2).. To understand the transdiagnostic role of death anxiety in mental health disorders. (3).. To understand current treatment approaches for directly targeting death anxiety, and the importance of doing so to improve long-term treatment outcomes.

negative: The Major Product of Porcine Transmissible Gastroenteritis Coronavirus Gene 3b Is an Integral Membrane Glycoprotein of 31 kDa Abstract The open reading frame potentially encoding a polypeptide of 27.7 kDa and located as the second of three ORFs (gene 3b) between the S and M genes in the genome of the Purdue strain of porcine transmissible gastroenteritis coronavirus (TGEV) was cloned and expressedin vitroto examine properties of the protein. Gene 3b has a postulated role in pathogenesis, but its truncated form in some laboratory-passaged strains of TGEV has led to the suggestion that it is not essential for virus replication. During synthesisin vitroin the presence of microsomes, the 27.7-kDa polypeptide became an integral membrane protein, retained its postulated hydrophobic N-terminal signal sequence, and underwent glycosylation on apparently two asparagine linkage sites to attain a final molecular mass of 31 kDa. A 20-kDa N-terminally truncated, nonglycosylated, nonanchored form of the protein was also made via an unknown mechanism. The existence of both transmembrane and soluble forms of the gene 3 product in the cell is suggested by immunofluorescence patterns showing both a punctated perinuclear and diffuse intracytoplasmic distribution. No gene 3b product was found on gradient-purified Purdue TGEV by a Western blotting procedure that would have detected as few as 4 molecules/virion, indicating the protein probably is not a structural component of the virion.

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: Tourism today: Why is it a global phenomenon embracing all our lives?

negative: Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19? In December 2019, a new coronavirus, named SARS-CoV-2, has emerged from China causing pneumonia outbreaks first in the Wuhan region and have now spread worldwide because of its probable high transmission efficiency. Due 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 therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin or ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococci infection, previously showed efficacy to inhibit the first stage of MERS-coronarivus viral cycle in human cells. This activity is conserved on the SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

negative: Significance of viral glycoproteins for infectivity and pathogenicity() Disease resulting from virus infection is a complex event depending on the close interaction of viral and cellular factors. Through the application of biochemical and genetic methods, it is now possible to gain an insight into the molecular basis of these interactions. Thus, it has been shown that the glycoproteins of enveloped viruses play a central role in the initiation of infection. They are responsible not only for the adsorption of virions to cellular receptors, but are also for the entry of the genome into the cell by the fusion of viral envelopes with cellular membranes. Evidence is growing that the fusogenic glycoproteins are frequently activated by cellular proteases. The structure of the proteins at the cleavage site and the availability of a suitable protease are critical for tissue tropism, spread of the virus in the infected organism and, thus, for pathogenicity. This will be demonstrated here by the example of the haemagglutinin of influenza viruses.

negative: A deductive approach to modeling the spread of COVID-19 Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), previously known as 2019-nCoV, is responsible for the atypical pneumonia pandemic designated as Coronavirus Disease 2019 (COVID-19). The confirmed number of cases continues to grow exponentially reaching 492,000 people in 175 countries as of March 25, 2020. 22,169 people (~4.5%) infected with SARS-COV-2 virus have died. We have developed an exponential regression model using the COVID-19 case data (Jan 22 - Mar 22, 2020). Our primary model uses designated Phase 1 countries, who exceed 2500 cases on Mar 22. The model is then applied to Phase 2 countries: those that escaped the initial Phase 1 global expansion of COVID-19. With the exception of stabilizing countries (South Korea, Japan, and Iran) all Phase 1 countries are growing exponentially, as per I2500(t)=120.4 × e0.238t, with a rate, r = 0.238 ± 0.068. Excluding China, the BRICS developing nations and Australia are in Phase 2. Case data from Phase 2 countries are following the model derived from Phase 1 countries. In the absence of measures employed to flatten the curve including social distancing, quarantine, and healthcare expansion, our model projects over 274,000 cases and 12,300 deaths in the US by Mar 31. India can expect 123,000 cases by April 16. By flattening the curve to the growth rate of stabilizing countries (r = 0.044 ± 0.062), the US would prevent 8,500 deaths by Mar 31, and India would prevent 5,500 deaths by April 16.

negative: El coronavirus causante del síndrome respiratorio de Oriente Medio

negative: Chapter 8 Changing how we think about infectious diseases Abstract As we learn more and more about the classes of organisms that infect humans, we are discovering that many organisms, including pathogenic organisms, may have a complex relationship with humans in which infection seldom results in the production disease. In some cases, infection may be just one biological event that occurs during a multievent process that develops sequentially, over time, and involves genetic and environmental factors that may vary among individuals. Consequently, the role of infectious organisms in the development of human disease may not meet all of the criteria normally required to determine when an organism can be called the cause of a disease. This chapter reviews the expanding role of infections in the development of human disease. We discuss prion diseases of humans, a fascinating example of an infectious disease-causing agent that is not a living organism. We also discuss the diseases of unknown etiology for which infectious organisms may play a role. In addition, this chapter reviews some of the misconceptions and recurring errors associated with the classification of infectious diseases that have led to misdiagnoses and have impeded our understanding of the role of organisms in the development of human diseases.

negative: COVID-19 Exposes Need for Progressive Criminal Justice Reform. Modeling conducted by the Centers for Disease Control and Prevention calculates that as many as 160 to 214 million people in the United States could become infected by the 2019 novel coronavirus (SARS-CoV-2, which causes the disease COVID-19) and that as many as 200 000 to 1.7 million may die from COVID-19.1 Prisons and jails are amplifiers of infectious diseases because of overcrowding and unsanitary living conditions and will most certainly contribute to these estimates. COVID-19 outbreaks have already been identified in New York City and Cook County, Illinois, jails, with infection rates at the Rikers Island jail complex far exceeding community rates. In response, correctional systems are implementing changes to mitigate the spread of COVID-19, including reducing jail and prison admissions and releasing people from facilities. In tandem, jails and prisons must also initiate facility-level policies to help stop the spread of COVID-19. (Am J Public Health. Published online ahead of print April 29, 2020: e1-e2. doi:10.2105/AJPH.2020.305707).

negative: Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.

negative: COVID-19 in Pregnancy: Consider Thromboembolic Disorders and Thromboprophylaxis

negative: Report of 5 nurses infecting COVID-19 during patient care: case Series Abstract Background The high prevalence of COVID-19 has been paied lots of attention all over the world. Nurses are in the first line against this infection and they placed in a high-risk situation. This study aimed to report COVID-19 infection during patients care among nures in the Mostafa Khomini Hospital, Ilam, Iran. In this hospital 125 nurses were enrolled in COVID-19 center. Findings In the present study 5 out of 125 nurses (4%) who enrolled in COVID-19 infection center, were infected with COVID-19. They were first positive for real-time PCR but the CT scan was positive for just one of them. None of the infected nurses were hospitalized and all of them preferred to be quarantine at home and receive the necessary care and treatment (Oseltamivir, Azithromycin and Kaletra. Conclusion This study showed that regardless of self caring, the nurses were exposed to COVID-19. Because at the the beginning of SARS-CoV-2 outbreak in Iran, there were no special protection against this infection.Therfore they were at risk for the COVID-19.This study also reported that receiving the necessary care and treatment at home was a good experience for nurses that can be used in some cases.

negative: KAPITEL 13 Infektionskrankheiten Zur Orientierung Infektionskrankheiten werden durch Pathogene verursacht, die sich im Wirt vermehren: Ektoparasiten, Helminthen, Protozoen, Pilze, Bakterien, Viren, Prionen. Infektionskrankheiten können alle Organe bzw. Organsysteme befallen. Entstehung und Verlauf werden durch Faktoren beeinflusst, die sich grob einteilen lassen in Erreger- und Wirtsfaktoren. Die Kenntnis und richtige Einschätzung dieser Faktoren sind entscheidend für Diagnostik und Therapie dieser Erkrankungen.

negative: Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?

negative: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.

negative: Tackling two pandemics: a plea on World Tuberculosis Day

negative: Prediction and analysis of Coronavirus Disease 2019 In December 2019, a novel coronavirus was found in a seafood wholesale market in Wuhan, China. WHO officially named this coronavirus as COVID-19. Since the first patient was hospitalized on December 12, 2019, China has reported a total of 78,824 confirmed CONID-19 cases and 2,788 deaths as of February 28, 2020. Wuhan's cumulative confirmed cases and deaths accounted for 61.1% and 76.5% of the whole China mainland , making it the priority center for epidemic prevention and control. Meanwhile, 51 countries and regions outside China have reported 4,879 confirmed cases and 79 deaths as of February 28, 2020. COVID-19 epidemic does great harm to people's daily life and country's economic development. This paper adopts three kinds of mathematical models, i.e., Logistic model, Bertalanffy model and Gompertz model. The epidemic trends of SARS were first fitted and analyzed in order to prove the validity of the existing mathematical models. The results were then used to fit and analyze the situation of COVID-19. The prediction results of three different mathematical models are different for different parameters and in different regions. In general, the fitting effect of Logistic model may be the best among the three models studied in this paper, while the fitting effect of Gompertz model may be better than Bertalanffy model. According to the current trend, based on the three models, the total number of people expected to be infected is 49852-57447 in Wuhan,12972-13405 in non-Hubei areas and 80261-85140 in China respectively. The total death toll is 2502-5108 in Wuhan, 107-125 in Non-Hubei areas and 3150-6286 in China respetively. COVID-19 will be over p robably in late-April, 2020 in Wuhan and before late-March, 2020 in other areas respectively.

negative: Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus. The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.

negative: Clinical Efficacy of Intravenous Immunoglobulin Therapy in Critical Patients with COVID-19: A multicenter retrospective cohort study Summary Background Coronavirus disease 2019 (COVID-19) has spread all over the world, causing more than 1.5 million infections and over ten thousands of deaths in a short period of time. However, little is known about its pathological mechanism, and there are still no clinical study reports on specific treatment. The purpose of this study is to determine the clinical efficacy of intravenous immunoglobulin (IVIG) therapy on COVID-19. Methods In this multicenter retrospective cohort study, adult critical COVID-19 patients (including severe type and critical type, according to the clinical classification defined by National Health Commission of China) in 8 government designated treatment center in China from Dec 23, 2019 to Mar 31, 2020 were enrolled. Demographic, clinical, treatment, and laboratory data, prognosis were extracted from electronic medical records, and IVIG was exposure factor. Primary outcomes were the 28 days and 60 days mortality, and secondary outcomes were the total length of in-hospital and the total duration of the disease. Meanwhile, the parameters of inflammation response and organ function were detected. The risk factors were determined by COX proportional hazards model. The subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Findings 325patients were included in this study, of whom 222 (68%) were severe type, 103 (32%) were critical type. 42 (13%) died in 28 days within hospitalization, total 54 (17%) died in 60 days, and 6 (3%) died in severe type, 48 (47%) died in critical type. 174 cases were used IVIG, and 151 cases were not. Compared with the baseline characteristics between two groups, the results showed that the patients in IVIG group had higher Acute Physiology and Chronic Health Evaluation (APACHII) score, Sequential Organ Failure Assessment (SOFA) score, IL-6 and lactate level, lower lymphocyte count and oxygenation index (all P<0.05). The 28 day and 60 day mortality did not improve with IVIG in overall patients. The in-hospital stay and the total duration of disease were longer in IVIG group (p<0.001). Risk factors were clinical classification (hazards ratio 0.126, 95% confidence interval 0.039-0.413, P=0.001), and using IVIG (hazards ratio 0.252, 95% confidence interval 0.107-0.591, P=0.002) with COX regression. Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28 day mortality, decrease the inflammatory response and improve some organ functions (all p<0.05), and 60-day mortality reduced significantly by using IVIG in the early stage (admission[≤]7 days) and with high dose (>15 g/d). Interpretation Early and high dose of IVIG therapy may improve the prognosis of COVID-19 patients only in critical type, which provides the clinical basis for the choice of treatment population and method of IVIG therapy for the SARS-CoV-2 infection. Keywords: SARS-COV-2, COVID-19, IVIG, clinical efficacy, mortality

negative: Estimating instant case fatality rate of COVID-19 in China Abstract Objective The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate instant case fatality rate and cure rate of COVID-19 in China. Methods We collected 82735 confirmed cases released officially by Chinese authorities from Dec 8, 2019 to April 18, 2020. The estimated diagnosis dates of deaths and cured cases were calculated based on median cure time or median death time of individual cases. Afterward, instant fatality rate was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. Results In China, the instant case fatality rate of COVID-19 was 3.8-14.6% from Jan 1 to Jan 17, and then gradually declined and stabilized at 5.7% in April. The average case fatality rate in China was 6.1%±2.9%. While, the case fatality rate was 1.0±0.4% in China except Hubei. The cure rates of COVID-19 were 93.9%±2.9% in China, and stabilized at 94.3%, while it was 99.0%±0.4% in China except Hubei. Conclusion The instant case fatality rate of COVID-19 in China was much higher than that in China except Hubei. The case fatality rate of COVID-19 in China was underestimated.

negative: How to protect the protectors: 10 lessons to learn for doctors fighting the COVID-19 coronavirus

negative: Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a rapid review BACKGROUND: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with respiratory virus diseases, and are currently being investigated in trials as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES: To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19. SEARCH METHODS: The protocol was pre-published with the Center for Open Science and can be accessed here: osf.io/dwf53 We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trials registries to identify ongoing studies and results of completed studies on 23 April 2020 for case-series, cohort, prospectively planned, and randomised controlled trials (RCTs). SELECTION CRITERIA: We followed standard Cochrane methodology and performed all steps regarding study selection in duplicate by two independent review authors (in contrast to the recommendations of the Cochrane Rapid Reviews Methods Group). We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulins. DATA COLLECTION AND ANALYSIS: We followed recommendations of the Cochrane Rapid Reviews Methods Group regarding data extraction and assessment. To assess bias in included studies, we used the assessment criteria tool for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events, and serious adverse events. MAIN RESULTS: We included eight studies (seven case-series, one prospectively planned, single-arm intervention study) with 32 participants, and identified a further 48 ongoing studies evaluating convalescent plasma (47 studies) or hyperimmune immunoglobulin (one study), of which 22 are randomised. Overall risk of bias of the eight included studies was high, due to: study design; small number of participants; poor reporting within studies; and varied type of participants with different severities of disease, comorbidities, and types of previous or concurrent treatments, including antivirals, antifungals or antibiotics, corticosteroids, hydroxychloroquine and respiratory support. We rated all outcomes as very low certainty, and we were unable to summarise numerical data in any meaningful way. As we identified case-series studies only, we reported results narratively. Effectiveness of convalescent plasma for people with COVID-19 The following reported outcomes could all be related to the underlying natural history of the disease or other concomitant treatment, rather than convalescent plasma. All-cause mortality at hospital discharge All studies reported mortality. All participants were alive at the end of the reporting period, but not all participants had been discharged from hospital by the end of the study (15 participants discharged, 6 still hospitalised, 11 unclear). Follow-up ranged from 3 days to 37 days post-transfusion. We do not know whether convalescent plasma therapy affects mortality (very low-certainty evidence). Improvement of clinical symptoms (assessed by respiratory support) Six studies, including 28 participants, reported the level of respiratory support required; most participants required respiratory support at baseline. All studies reported improvement in clinical symptoms in at least some participants. We do not know whether convalescent plasma improves clinical symptoms (very low-certainty evidence). Time to discharge from hospital Six studies reported time to discharge from hospital for at least some participants, which ranged from four to 35 days after convalescent plasma therapy. Admission on the intensive care unit (ICU) Six studies included patients who were critically ill. At final follow-up the majority of these patients were no longer on the ICU or no longer required mechanical ventilation. Length of stay on the ICU Only one study (1 participant) reported length of stay on the ICU. The individual was discharged from the ICU 11 days after plasma transfusion. Safety of convalescent plasma for people with COVID-19 Grade 3 or 4 adverse events The studies did not report the grade of adverse events after convalescent plasma transfusion. Two studies reported data relating to participants who had experienced adverse events, that were presumably grade 3 or 4. One case study reported a participant who had moderate fever (38.9 °C). Another study (3 participants) reported a case of severe anaphylactic shock. Four studies reported the absence of moderate or severe adverse events (19 participants). We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low-certainty evidence). Serious adverse events One study (3 participants) reported one serious adverse event. As described above, this individual had severe anaphylactic shock after receiving convalescent plasma. Six studies reported that no serious adverse events occurred. We are very uncertain whether or not convalescent plasma therapy affects the risk of serious adverse events (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified eight studies (seven case-series and one prospectively planned single-arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID-19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low-certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID-19; all studies were at high risk of bias and reporting quality was low. No RCTs or controlled non-randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here.

negative: Emerging Influenza and Psychosis: An Important Story in Psychological Medicine

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: O papel da atenção primária no combate ao Covid-19: impacto na saúde pública e perspectivas futuras A doença do novo Coronavírus (Covid-19) é causada pelo SARS-CoV-2 e representa o agente causador de uma doença potencialmente fatal que tem se revelado um problema de saúde pública global A pandemia causada pelo Covid-19 tem causado prejuízos severos nos sistemas de saúde em diversos países Diante do grande número de pessoas infectadas e da ausência de tratamento específico, várias nações têm enfrentado superlotação em seus hospitais Com a confirmação de casos desta doença no Brasil, várias ações têm sido tomadas por gestores públicos e privados, tanto a nível hospitalar quanto em nível de atenção primária, a fim de minimizar os impactos para o Sistema Único de Saúde (SUS) O presente artigo apresenta uma breve análise do papel da atenção primária na luta contra o Covid-19 em âmbito nacional, além do impacto em saúde pública e das futuras perspectivas Com base no grande número de pessoas infectadas no mundo e a experiência de diversos sistemas de saúde, torna-se imperativo a adaptação e adequação do SUS na condução de mecanismos de resposta para pandemia, sendo a atenção primária peça fundamental neste processo The new coronavirus (Covid-19) disease is caused by SARS-CoV-2 and represents the causative agent of a potentially fatal disease that has proved to be a global public health problem The pandemic caused by Covid-19 has caused severe damage to health systems in several countries In view of the large number of infected people and the lack of specific treatment, several nations have faced overcrowding in their hospitals With the confirmation of cases of this disease in Brazil, several actions have been taken by managers, both at the hospital level and at the level of primary care, in order to minimize the damage in the Unified Health System (SUS) This article presents a brief analysis of the role of primary care in the fight against Covid-19 at the national level, in addition to the impact on public health and future perspectives Based on the large number of infected people in the world and the experience of different health systems, it is imperative to adapt and adequation the SUS in conducting response mechanisms for the pandemic, with primary care being a fundamental part of this process La enfermedad del nuevo coronavirus (Covid-19) es causada por el SARS-CoV-2 y representa el agente causal de una enfermedad potencialmente mortal que ha demostrado ser un problema global de salud pública La pandemia causada por Covid-19 ha causado graves daños a los sistemas de salud en varios países En vista de la gran cantidad de personas infectadas y la falta de tratamiento específico, varias naciones han enfrentado hacinamiento en sus hospitales Con la confirmación de los casos de esta enfermedad en Brasil, los gerentes han tomado varias medidas, tanto a nivel hospitalario como a nivel de atención primaria, para minimizar el daño en el Sistema Único de Salud (SUS) Este artículo presenta un breve análisis del papel de la atención primaria en la lucha contra Covid-19 en todo el país, además del impacto en la salud pública y las perspectivas futuras Basado en la gran cantidad de personas infectadas en el mundo y la experiencia de diferentes sistemas de salud, es imperativo adaptar y adaptar el SUS en la conducción de mecanismos de respuesta a la pandemia, siendo la atención primaria una parte fundamental de este proceso

negative: Differential Activities of Cellular and Viral Macro Domain Proteins in Binding of ADP-Ribose Metabolites Abstract Macro domain is a highly conserved protein domain found in both eukaryotes and prokaryotes. Macro domains are also encoded by a set of positive-strand RNA viruses that replicate in the cytoplasm of animal cells, including coronaviruses and alphaviruses. The functions of the macro domain are poorly understood, but it has been suggested to be an ADP-ribose-binding module. We have here characterized three novel human macro domain proteins that were found to reside either in the cytoplasm and nucleus [macro domain protein 2 (MDO2) and ganglioside-induced differentiation-associated protein 2] or in mitochondria [macro domain protein 1 (MDO1)], and compared them with viral macro domains from Semliki Forest virus, hepatitis E virus, and severe acute respiratory syndrome coronavirus, and with a yeast macro protein, Poa1p. MDO2 specifically bound monomeric ADP-ribose with a high affinity (K d =0.15 μM), but did not bind poly(ADP-ribose) efficiently. MDO2 also hydrolyzed ADP-ribose-1″ phosphate, resembling Poa1p in all these properties. Ganglioside-induced differentiation-associated protein 2 did not show affinity for ADP-ribose or its derivatives, but instead bound poly(A). MDO1 was generally active in these reactions, including poly(A) binding. Individual point mutations in MDO1 abolished monomeric ADP-ribose binding, but not poly(ADP-ribose) binding; in poly(ADP-ribose) binding assays, the monomer did not compete against polymer binding. The viral macro proteins bound poly(ADP-ribose) and poly(A), but had a low affinity for monomeric ADP-ribose. Thus, the viral proteins do not closely resemble any of the human proteins in their biochemical functions. The differential activity profiles of the human proteins implicate them in different cellular pathways, some of which may involve RNA rather than ADP-ribose derivatives.

negative: Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020 Abstract Background There’s an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. Methods 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. Results The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. Conclusions Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.

negative: Global service‐learning and COVID‐19—What the future might look like? The novel coronavirus disease (COVID-19) pandemic has disrupted travel and caused marked death and disability globally. The economic impact of this change has forced universities to operate differently in how they conduct their operations and deliver education to students (Jackson et al. 2020). Leveraging digital modalities has been crucial in achieving business continuity.

negative: Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID-19) and the SARS-CoV-2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.

negative: Long-term trends in seasonality of mortality in urban Madagascar: the role of the epidemiological transition Background: Seasonal patterns of mortality have been identified in Sub-Saharan Africa but their changes over time are not well documented. Objective: Based on death notification data from Antananarivo, the capital city of Madagascar, this study assesses seasonal patterns of all-cause and cause-specific mortality by age groups and evaluates how these patterns changed over the period 1976–2015. Methods: Monthly numbers of deaths by cause were obtained from death registers maintained by the Municipal Hygiene Office in charge of verifying deaths before the issuance of burial permits. Generalized Additive Mixed regression models (GAMM) were used to test for seasonality in mortality and its changes over the last four decades, controlling for long-term trends in mortality. Results: Among children, risks of dying were the highest during the hot and rainy season, but seasonality in child mortality has significantly declined since the mid-1970s, as a result of declines in the burden of infectious diseases and nutritional deficiencies. In adults aged 60 and above, all-cause mortality rates are the highest in the dry and cold season, due to peaks in cardiovascular diseases, with little change over time. Overall, changes in the seasonality of all-cause mortality have been driven by shifts in the hierarchy of causes of death, while changes in the seasonality within broad categories of causes of death have been modest. Conclusion: Shifts in disease patterns brought about by the epidemiological transition, rather than changes in seasonal variation in cause-specific mortality, are the main drivers of trends in the seasonality of all-cause mortality.

negative: Geographies of the COVID-19 pandemic The spread of the novel coronavirus (SARS-CoV-2) has resulted in the most devastating global public health crisis in over a century. At present, over 7 million people from around the world have contracted the Coronavirus Disease 2019 (COVID-19), leading to more than 400,000 deaths globally. The global health crisis unleashed by the COVID-19 pandemic has been compounded by political, economic, and social crises that have exacerbated existing inequalities and disproportionately affected the most vulnerable segments of society. The global pandemic has had profoundly geographical consequences, and as the current crisis continues to unfold, there is a pressing need for geographers and other scholars to critically examine its fallout. This introductory article provides an overview of the current special issue on the geographies of the COVID-19 pandemic, which includes 42 commentaries written by contributors from across the globe. Collectively, the contributions in this special issue highlight the diverse theoretical perspectives, methodological approaches, and thematic foci that geographical scholarship can offer to better understand the uneven geographies of the Coronavirus/COVID-19.

negative: Global Trends in Epidemiology of Coronavirus Disease 2019 (COVID-19) In December 2019, suddenly 54 cases of viral pneumonia emerged in Wuhan, China, caused by some unknown microorganism. The virus responsible for these pneumonia infections was identified as novel coronavirus of the family Coronaviridae. The novel coronavirus was renamed as COVID-19 by WHO. Infection from the virus has since increased exponentially and has spread all over the world in more than 196 countries. The WHO has declared a Public Health Emergency of International Concern due to the outbreak of COVID-19. The virus is highly infectious and can cause human-to-human transmission. Every 24 h, cases of COVID-19 increase severalfolds. The WHO is monitoring the SARS-CoV-2 spread very closely via a global surveillance system. The current situation demands the enforcement of strict laws which would help in inhibiting the further spread of COVID-19. Social distancing, international travel restrictions to affected countries, and hygiene are three important ways to nullify SARS-CoV-2.Government and private organizations need to come forward and work together during this pandemic. Public awareness, social distancing, and sterilization must be maintained to neutralize the viral infection, especially in major hot spots.

negative: Transmission potential of COVID-19 in South Korea Since the first identified individual of 2019 novel coronavirus (COVID-19) infection on Jan 20, 2020 in South Korea, the number of confirmed cases rapidly increased. As of Feb 26, 2020, 1,261 cases of COVID-19 including 12 deaths were confirmed in South Korea. Using the incidence data of COVID-19, we estimate the reproduction number at 1.5 (95% CI: 1.4-1.6), which indicates sustained transmission and support the implementation of social distancing measures to rapidly control the outbreak.

negative: Excess mortality during COVID-19 in five European countries and a critique of mortality analysis data INTRODUCTION The COVID-19 pandemic is an ongoing event disrupting lives, health systems, and economies worldwide. Clear data about the pandemic's impact is lacking, namely regarding mortality. This work aims to study the impact of COVID-19 through the analysis of all-cause mortality data made available by different European countries, and to critique their mortality surveillance data. METHODS European countries that had publicly available data about the number of deaths per day/week were selected (England and Wales, France, Italy, Netherlands and Portugal). Two different methods were selected to estimate the excess mortality due to COVID19: (DEV) deviation from the expected value from homologue periods, and (RSTS) remainder after seasonal time series decomposition. We estimate total, age- and gender-specific excess mortality. Furthermore, we compare different policy responses to COVID-19. RESULTS Excess mortality was found in all 5 countries, ranging from 10.6% in Portugal (DEV) to 98.5% in Italy (DEV). Furthermore, excess mortality is higher than COVID-attributed deaths in all 5 countries. DISCUSSION The impact of COVID-19 on mortality appears to be larger than officially attributed deaths, in varying degrees in different countries. Comparisons between countries would be useful, but large disparities in mortality surveillance data could not be overcome. Unreliable data, and even a lack of cause-specific mortality data undermine the understanding of the impact of policy choices on both direct and indirect deaths during COVID-19. European countries should invest more on mortality surveillance systems to improve the publicly available data.

negative: Lessons drawn from China and South Korea for managing COVID-19 epidemic: insights from a comparative modeling study We conducted a comparative study of COVID-19 epidemic in three different settings: mainland China, the Guangdong province of China and South Korea, by formulating two disease transmission dynamics models incorporating epidemic characteristics and setting-specific interventions, and fitting the models to multi-source data to identify initial and effective reproduction numbers and evaluate effectiveness of interventions. We estimated the initial basic reproduction number for South Korea, the Guangdong province and mainland China as 2.6 (95% confidence interval (CI): (2.5, 2.7)), 3.0 (95%CI: (2.6, 3.3)) and 3.8 (95%CI: (3.5,4.2)), respectively, given a serial interval with mean of 5 days with standard deviation of 3 days. We found that the effective reproduction number for the Guangdong province and mainland China has fallen below the threshold 1 since February 8th and 18th respectively, while the effective reproduction number for South Korea remains high, suggesting that the interventions implemented need to be enhanced in order to halt further infections. We also project the epidemic trend in South Korea under different scenarios where a portion or the entirety of the integrated package of interventions in China is used. We show that a coherent and integrated approach with stringent public health interventions is the key to the success of containing the epidemic in China and specially its provinces outside its epicenter, and we show that this approach can also be effective to mitigate the burden of the COVID-19 epidemic in South Korea. The experience of outbreak control in mainland China should be a guiding reference for the rest of the world including South Korea.

negative: Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103(+) and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.

negative: A pandemic at the Tunisian scale. Mathematical modelling of reported and unreported COVID-19 infected cases Starting from the city of Wuhan in China in late December 2019, the pandemic quickly spread to the rest of the world along the main intercontinental air routes. At the time of writing this article, there are officially about five million infections and more than 300 000 deaths. Statistics vary widely from country to country, revealing significant differences in anticipation and management of the crisis. We propose to examine the COVID-19 epidemic in Tunisia through mathematical models, which aim to determine the actual number of infected cases and to predict the course of the epidemic. As of May 11, 2020, there are officially 1032 COVID-19 infected cases in Tunisia. 45 people have died. Using a mathematical model based on the number of reported infected cases, the number of deaths, and the effect of the 18-day delay between infection and death, this study estimates the actual number of COVID-19 cases in Tunisia as 2555 cases. This paper analyses the evolution of the epidemic in Tunisia using population dynamics with an SEIR model combining susceptible cases S(t), asymptomatic infected cases A(t), reported infected cases V (t), and unreported infected cases U(t). This work measures the basic reproduction number R0, which is the average number of people infected by a COVID-19 infected person. The model predicts an R0 = 2.73. Strict containment measures have led to a significant reduction in the reproduction rate. Contact tracing and respect for isolation have an impact: at the current time, we compute that Tunisia has an Rt = 0.42 (95% CI 0.14-0.70). These values depend on physical separation and can vary over time depending on the management of suspicious cases. Their objective estimation and the study of their evolution are however necessary to understand the pandemic and to reduce their unintended damage (due to an absence of symptoms, or the confusion of certain symptoms with less contagious diseases, or unavailable or unreliable tests).

negative: Common Pitfalls in the Interpretation of COVID-19 Data and Statistics Policymakers, experts and the general public heavily rely on the data that are being reported in the context of the coronavirus pandemic. Daily data releases on confirmed COVID-19 cases and deaths provide information on the course of the pandemic.

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: Pains and Gains from China's Experiences with Emerging Epidemics: From SARS to H7N9 Over the recent decades, China experienced several emerging virus outbreaks including those caused by the severe acute respiratory syndrome- (SARS-) coronavirus (Cov), H5N1 virus, and H7N9 virus. The SARS tragedy revealed faults in China's infectious disease prevention system, propelling the Chinese government to enact reforms that enabled better combating of the subsequent H1N1 and H7N9 avian flu epidemics. The system is buttressed by three fundamental, mutually reinforcing components: (1) enduring government administration reforms, including legislation establishing a unified public health emergency management system; (2) prioritized funding for biotechnology and biomedicine industrialization, especially in the areas of pathogen identification, drug production, and the development of vaccines and diagnostics; and (3) increasing investment for public health and establishment of a rapid-response infectious diseases prevention and control system. China is now using its hard-gained experience to support the fight against Ebola in Africa and the Middle East Respiratory Syndrome in its own country.

negative: A dual-centre observational review of hospital based palliative care in patients dying with COVID-19 Abstract The current Covid-19 pandemic has put significant strain on all aspects of healthcare delivery, including palliative care services. Given the high mortality from this disease, particularly in the more vulnerable members of society, it is important to examine how best to deliver a high standard of end of life care during this crisis. This case series collected data from two acute hospitals examining the management of patients diagnosed with Covid-19 who subsequently died (n=36) and compared this to national and local end of life audit data for all other deaths. Our results demonstrated a shorter dying phase (38.25 hours vs 74 hours) and higher rates of syringe driver use (72% vs 33% in local audits), although with similar average mediation doses. Of note was the significant heterogeneity in the phenotype of deterioration in the dying phase, two distinct patterns emerged, with one group demonstrating severe illness with a short interval between symptom onset and death and another group presenting with a more protracted deterioration. This brief report suggests a spectrum of mode of dying. Over all the cohort reflects previously described experiences, with increased frailty (median Clinical Frailty Scale score of 5) and extensive comorbidity burden. This brief report provides clinicians with a contemporaneous overview of our experience, knowledge and pattern recognition when caring for people with Covid-19 and highlights the value of proactive identification of patients and risk of deterioration and palliation.

negative: COVID-19: An Update on the Epidemiological, Genomic Origin, Phylogenetic study, India centric to Worldwide current status The pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study.

negative: Does communicable diseases (including COVID-19) may increase global poverty risk? A cloud on the horizon Coronavirus epidemic can push millions of people in poverty. The shortage of healthcare resources, lack of sanitation, and population compactness leads to an increase in communicable diseases, which may increase millions of people add in a vicious cycle of poverty. The study used the number of factors that affect poverty incidence in a panel of 76 countries for a period of 2010–2019. The dynamic panel GMM estimates show that the causes of death by communicable diseases, chemical-induced carbon and fossil fuel combustion, and lack of access to basic hand washing facilities menace to increase poverty headcounts, whereas, an increase in healthcare expenditures substantially decreases poverty headcounts across countries. Further, the results show the U-shaped relationship between economic growth and poverty headcounts, as economic growth first decreases and later increase poverty headcount due to rising healthcare disparities among nations. The causality estimates show that lack of access to basic amenities lead to increase of communicable diseases including COVID-19 whereas chemical-induced carbon and fossil fuel emissions continue to increase healthcare expenditures and economic growth in a panel of selected countries. The rising healthcare disparities, regional conflicts, and public debt burden further ‘hold in the hand’ of communicable diseases that push millions of people in the poverty trap.

negative: Spiking the MERS-coronavirus receptor A novel coronavirus, the Middle East respiratory syndrome coronavirus, recently emerged through zoonotic transmission, causing a severe lower respiratory tract infection in humans. In two recent papers, one published in Cell Research, the crystal structure of the viral receptor-binding domain in complex with the host CD26/dipeptidyl peptidase 4 receptor has now been characterized.

negative: Epigenetic transmission of feline infectious peritonitis Feline Infectious Peritonitis (F.I.P.) was diagnosed in the kittens of two successive litters born to a female presumed also infected. At the same time, the two fathers and the other subjects of the cattery remained asymptomatic of F.I.P. The clinical observations, supported by electrophoretic data, suggest the possibility of a direct transmission of the disease by the mother to her offspring, either by the transplacentary pathway (epigenetic transmission) or via the milk.

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: Bayesian Network Analysis of Covid-19 data reveals higher Infection Prevalence Rates and lower Fatality Rates than widely reported Widely reported statistics on Covid-19 across the globe fail to take account of both the uncertainty of the data and possible explanations for this uncertainty. In this paper we use a Bayesian Network (BN) model to estimate the Covid-19 infection prevalence rate (IPR) and infection fatality rate (IFR) for different countries and regions, where relevant data are available. This combines multiple sources of data in a single model. The results show that Chelsea Mass. USA and Gangelt Germany have relatively higher infection prevalence rates (IPR) than Santa Clara USA, Kobe, Japan and England and Wales. In all cases the infection prevalence is significantly higher than what has been widely reported, with much higher community infection rates in all locations. For Santa Clara and Chelsea, both in the USA, the most likely IFR values are 0.3-0.4%. Kobe, Japan is very unusual in comparison with the others with values an order of magnitude less than the others at, 0.001%. The IFR for Spain is centred around 1%. England and Wales lie between Spain and the USA/German values with an IFR around 0.8%. There remains some uncertainty around these estimates but an IFR greater than 1% looks remote for all regions/countries. We use a Bayesian technique called "virtual evidence" to test the sensitivity of the IFR to two significant sources of uncertainty: survey quality and uncertainty about Covid-19 death counts. In response the adjusted estimates for IFR are most likely to be in the range 0.3%-0.5%.

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: Utilitarianism and the Pandemic There are no egalitarians in a pandemic. The scale of the challenge for health systems and public policy means that there is an ineluctable need to prioritise the needs of the many. It is impossible to treat all citizens equally, and a failure to carefully consider the consequences of actions could lead to massive preventable loss of life. In a pandemic there is a strong ethical need to consider how to do most good overall. 1. Triage: which patients should receive access to a ventilator if there is overwhelming demand outstripping supply? 2. Lockdown: How should countries decide when to implement stringent social restrictions, balancing preventing deaths from COVID‐19 with causing deaths and reducing in wellbeing from other causes? Our aim is not to argue that utilitarianism is the only relevant ethical theory, or in favour of a purely utilitarian approach. However, clearly considering which options will do the most good overall will help societies identify and consider the necessary cost of other values. Societies may choose either to embrace or not to embrace the utilitarian course, but with a clear understanding of the values involved and the price they are willing to pay.

negative: Epidemiologische Grundlagen nosokomialer Infektionen Viele Faktoren tragen zu erhöhten nosokomialen Infektionsraten bei. Der Anteil alter Patienten mit chronischen Krankheiten und Immunsupprimierter steigt. Fortschritte in Diagnostik und Therapie resultieren immer häufiger in invasiven Eingriffen. Antibiotikaresistenzen und Folgen nosokomialer Infektionen erfordern daher eine verlässliche Epidemiologie. Konsequenzen nosokomialer Infektionen betreffen einerseits Patienten (Morbidität und Letalität), aber auch das Gesundheitswesen, dem zusätzliche, teilweise vermeidbare finanzielle Belastungen entstehen.

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: A statistical forecast of LOW mortality (< 400,000 deaths) due to COVID-19, for the whole WORLD. OBJECTIVE: To forecast the death toll of COVID-19 in the whole world by fitting the time series of reported deaths with a parametric equation (integrated Gaussian equation) related to Farr s law. DATA: The time series of cumulative deaths due to COVID-19 produced by John Hopkins University and stored in a github repository. RESULTS: The projected total death toll will be 261680 (392520 to 183176) which represents the 0.003 % of world population. This number amounts to 0.054 deaths per 1000, while the mean in the world (all causes) is 7.7. The daily peak of deaths (7270 (+/-500)) happened the 15 (+/- 3) of April, meaning that we are in descending curve of the pandemic. The outbreak will end completely the 23th (+/-3) of June. However, already on 9th (+/- 3) of May, 2 sigma; (95.45%) of the deaths will have be occured. The projected death toll is much lower (5-10 times) than those forecasted by the Imperial College Group (ICG) even considering the best scenario of total suppression of virus transmission. Using actual mortality rates it is possible to back calculate which number of infected individuals would produce such mortality. The death toll arises from a number of infected individuals between 53 (worst case) and 3.3 million. The calculated number of infected individuals is significantly lower than that calculated by ICG (227.5 millions) with suppression.

negative: Cost-Effectiveness Analysis of Influenza A (H1N1) Chemoprophylaxis in Brazil Background: Oseltamivir and zanamivir are recommended for treating and preventing influenza A (H1N1) worldwide. In Brazil, this official recommendation lacks an economic evaluation. Our objective was to assess the efficiency of influenza A chemoprophylaxis in the Brazilian context. Methods: We assessed the cost-effectiveness of oseltamivir and zanamivir for prophylaxis of influenza for high risk population, compared to no prophylaxis, in the perspective of Brazilian public health system. Quality-adjusted life years (QALY) and effectiveness data were based on literature review and costs in Brazilian real (BRL) were estimated from official sources and micro-costing of 2016’s H1N1 admissions at a university hospital. We used a decision-tree model considering prophylaxis and no prophylaxis and the probabilities of H1N1, ambulatory care, admission to hospital, intensive care, patient discharge, and death. Adherence and adverse events from prophylaxis were included. Incremental cost-effectiveness ratio was converted to 2016 United States dollar (USD). Uncertainty was assessed with univariated and probabilistic sensitivity analysis. Results: Adherence to prophylaxis was 0.70 [95% confidence interval (CI) 0.54; 0.83]; adverse events, 0.09 (95% CI 0.02; 0.18); relative risk of H1N1 infection in chemoprophylaxis, 0.43 (95% CI 0.33; 0.57); incidence of H1N1, 0.14 (95% CI 0.11; 0.16); ambulatory care, 0.67 (95% CI 0.58; 0.75); hospital admission, 0.43 (CI 95% 0.39; 0.42); hospital mortality, 0.14 (CI 95% 0.12; 0.15); intensive care unit admission, 0.23 (95% CI 0.20; 0.27); and intensive care mortality, 0.40 (95% CI 0.29; 0.52). QALY in H1N1 state was 0.50 (95% CI 0.46; 0.53); in H1N1 inpatients, 0.23 (95% CI 0.18; 0.28); healthy, 0.885 (95% CI 0.879; 0.891); death, 0. Adverse events estimated to affect QALY in –0.185 (95% CI –0.290; –0.050). Cost for chemoprophylaxis was BRL 39.42 [standard deviation (SD) 17.94]; ambulatory care, BRL 12.47 (SD 5.21); hospital admission, BRL 5,727.59 (SD 7,758.28); intensive care admission, BRL 19,217.25 (SD 7,917.33); and adverse events, BRL 292.05 (SD 724.95). Incremental cost-effectiveness ratio was BRL –4,080.63 (USD –1,263.74)/QALY and –982.39 (USD –304.24)/H1N1 prevented. Results were robust to sensitivity analysis. Conclusion: Chemoprophylaxis of influenza A (H1N1) is cost-saving in Brazilian health system context.

negative: COVID-19 Exposes Need for Progressive Criminal Justice Reform

negative: Chapter 13 Animals and Human Health Where Do They Meet? ∗ Abstract Human health and animal health are closely intertwined. We share hundreds of diseases with animals, and they are vectors for many diseases that assail humans—but, at the same time, they are essential to many treatments and cures. We discuss in this chapter various aspects of intimate relationship between human and animal health, giving examples of the importance of multidisciplinary studies in understanding these connections and the fundamental aspects of strategies for promoting the health and well-being of both groups.